2023 Fiscal Year Final Research Report
Investigation of the effects of aging of the gut microbiome on the development and rupture of cerebral aneurysms and the search for novel therapies.
Project/Area Number |
21K16608
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Osaka University |
Principal Investigator |
Kadono Yoshinori 大阪大学, 大学院医学系研究科, 招へい教員 (60770675)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | subarachnoid hemorrage / cerebral aneurysm / gut microbeome / くも膜下出血 / 加齢マウス / 腸内細菌叢 |
Outline of Final Research Achievements |
To investigate the effect of aging gut microbiome on the severity of subarachnoid hemorrhage, we performed an experiment to induce subarachnoid hemorrhage in old mice transplanted with stool from young mice, in which the gut microbiome was altered by transplantation of stool. Immunostaining and FACS revealed that the mortality rate within 24 hours after induction of subarachnoid hemorrhage decreased after stool transplantation, and the degree of early brain injury was also attenuated after stool transplantation. In addition, the differences in gut microbiome observed in stool samples from patients with unruptured aneurysms and patients with subarachnoid hemorrhage caused by ruptured cerebral aneurysms, as reported from our laboratory, were examined using single nucleotide polymorphisms and polygenic risk scores of blood samples among the same patients, suggesting the possibility of assessing the risk of rupture of cerebral aneurysms.
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Free Research Field |
Cerebral vascular disease
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Academic Significance and Societal Importance of the Research Achievements |
本研究の成果として、これまでに指摘されてきた高齢者における破裂脳動脈瘤によるくも膜下出血の重症化や予後不良の因子として、腸内細菌叢の老化が関係していることが判明した。また、年齢や性別、瘤の大きさ、部位などでしか予測し得なかった未破裂脳動脈瘤の破裂率に、腸内細菌叢やSNPといった新たな尺度を加え、より高い精度で破裂予測ができるようになることが期待できる。 また、これまでは外科的介入で破裂予防をするしかなかったくも膜下出血への防御策が、腸内細菌叢の操作で、破裂予防と破裂時の重症化予防を同時に行える新しいアプローチへの道がひらけば、医療経済的にも高齢者などへの低侵襲な介入としても期待できる。
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