2020 Fiscal Year Final Research Report
The alleviation of hepatic ischemia-reperfusion injury by modulating gut microbiota
| Project/Area Number |
19K24012
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0905:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Keywords | 肝虚血再灌流障害 / 抗生剤 / 肝移植 |
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| Outline of Final Research Achievements |
We aimed to determine whether rifaximin (RFX) pretreatment for liver transplant recipients alleviates liver ischemia-reperfusion injury. In the experimental arm, livers from BALB/c mice were transplanted to allogeneic C57BL/6 mice after 18 h of cold storage, followed by liver/blood sampling at 6 h post-reperfusion. RFX pretreatment for recipient mice alleviated hepatocellular damage, as evidenced by decreased serum transaminase levels, suppressed frequency of TUNEL-positive dead cells, inhibited hepatic macrophage/neutrophil infiltration, whereas supplemented fecal microbiota transplant diminished hepatoprotective influences of rifaximin pretreatment. In the clinical arm, we retrospectively analyzed 87 living donor liver transplant recipients. Recipients pretreated with RFX prior to liver transplantation exhibited better patient survival, graft survival and rejection-free graft survival.
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| Free Research Field |
消化器外科
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| Academic Significance and Societal Importance of the Research Achievements |
肝虚血再灌流障害は術後肝不全やグラフト拒絶の要因となるため，その予防は移植医療における重要な課題である。本研究では，非吸収性の抗生剤であり長期間の投与が比較的安全に行えることが報告されているリファキシミンが，マウス肝移植モデルにおいて虚血再灌流障害を緩和することを示した。臨床における肝移植レシピエントは術後に免疫抑制剤による治療を要するため，吸収性の抗生剤を術前のレシピエントに長期間投与することは，耐性菌の出現や難治性感染症を引き起こす可能性が危惧される。そのため，非吸収性で長期間投与が可能なリファキシミンによる肝保護効果が示された本研究は，今後の臨床応用の礎となりうる考えられる。
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