2020 Fiscal Year Final Research Report
Comprehensive analysis and interventional approach for intestinal dysbisosi in GVHD
| Project/Area Number |
17H04206
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | 腸内細菌 / 造血幹細胞移植 / GVHD |
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| Outline of Final Research Achievements |
We compared association of intestinal microbial ecology and outcomes of allogeneic hematpoietic stem cell transplantation. In mouse models, changes in microflora posttransplat were associated with GVHD severity and survival. Administration of wnt agonist R-spondin1 restored intestinal microflora and ameliorated GVHD. An international cooperative study showed that changes in intestinal microflora were associated with GVHD severity and mortality, irrespective of ethnicity. Overgrowth of Enterococcus was assocaited with poor transplant outcomes. These largest studies ever demosntrate that composition of the posttransplant microbiota could be associated with transplant outcomes.
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| Free Research Field |
血液内科学
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| Academic Significance and Societal Importance of the Research Achievements |
骨髄移植をはじめとする造血幹細胞移植は難治性の白血病など、血液がんや再生不良性貧血などに対する根治的治療法として普及している。しかし、その最重要の合併症である移植片対宿主病(GVHD)のより有効な治療法の開発によって、さらに移植の成績を向上させることができる。本研究では移植後の腸内細菌叢と移植成績の関連を検討した。その結果、移植後には腸内細菌叢の多様性が喪失し、特定の細菌種の増加がみられた。この変化は欧米人と日本人で同等であった。腸内細菌叢の変化が高度な例ではGVHDの重症化、死亡率の増加がみられた。腸内細菌叢を回復させることで移植成績の向上が期待できる。
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