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2023 Fiscal Year Final Research Report

Research on microbiome-gut axis in initial pathogenesis of Parkinson's disease

Research Project

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Project/Area Number 22K19512
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

Saiki Shinji  筑波大学, 医学医療系, 教授 (00339996)

Co-Investigator(Kenkyū-buntansha) 小林 俊輔  帝京大学, 医学部, 教授 (30579272)
石川 大  順天堂大学, 医学部, 准教授 (30622675)
松本 光晴  協同乳業株式会社研究所, 研究所, 主幹研究員 (50505972)
鎌形 康司  順天堂大学, 医学部, 准教授 (60568153)
Project Period (FY) 2022-06-30 – 2024-03-31
Keywordsパーキンソン病 / 腸内細菌叢
Outline of Final Research Achievements

The pathological finding common to all cases of Parkinson's disease (PD) is Lewy bodies, which are intracellular inclusions primarily composed of alpha-synuclein (aSyn) in substantia nigra neurons. From the early stages of the disease, aSyn deposits in the olfactory nerves and enteric nervous system terminals, propagating along axons within the central nervous system. Although the involvement of intestinal inflammation has been suggested as the initial trigger for aSyn deposition, the molecular mechanisms remain unclear. This study aimed to elucidate how the deposition of aSyn in enteric nerve terminals, which is considered a cause of PD onset, is influenced by changes in gut microbiota. Initially, a reverse analysis method was employed to identify metabolite changes directly associated with aSyn pathology through fecal metabolome analysis and to elucidate the causative bacteria.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

2年間の研究期間中である、2023年1月1日に研究代表者は順天堂大学大学院医学研究科から筑波大学医学医療系に異動した。そのため、筑波大学にて改めて特定臨床研究の申請手続きを実施している。
当初の予定通り、パーキンソン病・健常者の末梢血液サンプル・糞便サンプルなどの集積を進めた。現在血漿・糞便メタボローム解析データ、ショットガンメタゲノム解析データの統合的解析を進めている。これらにより、PD初期病変の起点となる細菌叢変化を同定し、ノトバイオートマウスでの解析に進む予定である。

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Published: 2025-01-30  

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