2023 Fiscal Year Final Research Report

Development of a new therapy to prevent rupture of cerebral aneurysms by targeting gut microbiome

Research Project

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Project/Area Number	21K09072
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55060:Emergency medicine-related
Research Institution	Osaka University
Principal Investigator	Nakagawa Ryota 大阪大学, 医学部附属病院, 医員 (50889920)
Co-Investigator(Kenkyū-buntansha)	中村元大阪大学, 大学院医学系研究科, 講師 (80533794) 高垣匡寿大阪大学, 大学院医学系研究科, 助教 (70724433) 竹中朋文大阪大学, 医学部附属病院, 医員 (60869527) 井筒伸之大阪大学, 医学部附属病院, 医員 (20834170) 川端修平大阪大学, 大学院医学系研究科, 招へい教員 (20764062) 松井雄一大阪大学, 医学部附属病院, 医員 (10764061)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	腸内細菌叢 / くも膜下出血
Outline of Final Research Achievements	A case-control analysis of gut microbiome using metagenomic shotgun sequencing on stool samples from patients with unruptured intracranial aneurysms and subarachnoid hemorrhage: significant differences were found between the two groups for five bacterial species, and a sensitivity analysis including various covariates showed similar results. Furthermore, polygenic risk score (PRS) analysis based on external genome-wide association analysis results showed no difference between the two groups of unruptured and ruptured intracranial aneurysms, although the PRS itself has disease predictive ability in terms of intracranial aneurysm possession when compared with the healthy control group. On the other hand, gut microbiome was not reproducibly associated with PRS, suggesting that it may be a factor associated with unruptured and ruptured intracranial aneurysms, independent of genetic factors. These results are currently being submitted for publication.
Free Research Field	脳血管障害
Academic Significance and Societal Importance of the Research Achievements	これまで報告されている脳動脈瘤に関連したGWASの結果によると、脳動脈瘤全体の解析でSNP-based heritabilityは20-30％前後だが未破裂脳動脈瘤と破裂脳動脈瘤の間に有意な差のある領域は認められておらず、未破裂と破裂を規定する遺伝的因子は同定されていない。我々が今回同定した菌種は脳動脈瘤の遺伝因子と独立した疾患関連因子であると考えられ、環境因子が脳動脈瘤を未破裂から破裂に変化させることが示唆された。これまで脳動脈瘤の破裂を予防する治療は確立されていないが、腸内細菌叢を標的とした治療はくも膜下出血の発症を減少させうるという社会的意義の大きい研究成果が得られたと考える。