Roles of Fusobacterium nucleatum in Systemic Inflammations by Cancer Chemotherapy

• Project/Area Number: 19K08839
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokushima
• Principal Investigator: NAKAMURA Shingen 徳島大学, 大学院医歯薬学研究部(医学域), 特任准教授 (10511321)
• Co-Investigator(Kenkyū-buntansha): 村上 圭史 川崎医療福祉大学, 医療技術学部 臨床栄養学科, 教授 (10335804) ; 日野出 大輔 徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (70189801)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: Fusobacterium nucleatum / secretory IgA / 発熱性好中球減少症 / Fusobacterium

Outline of Research at the Start

がんの発症や化学療法における口腔内細菌叢の役割は十分には明らかになっていない。我々はFusobacterium nucleatumが発熱性好中球減少症の発症に寄与することを見いだした。本研究では、Fusobacterium nucleatumに着目し、化学療法や造血幹細胞移植時の全身性感染症やGVHDなどの炎症惹起、血管内皮障害、がん微小環境等に対する影響の実態を明らかにするとともに、Fusobacteriumを定量する簡便な測定系の開発を目指す。

Outline of Final Research Achievements

ROS production was enhanced when anticancer drugs such as melphalan were added to the oral epithelial cell line TR146, and it was further enhanced when Fusobacterium nucleatum (Fuso) was added. We attempted to detect Fuso from blood culture bottles by PCR and anti-Fuso antibodies in serum and saliva by ELISA (using plates coated with Fuso), but it was difficult to measure accurately due to sensitivity and nonspecific reactions. As a clinical study, we collected saliva and tongue coating before chemotherapy in patients with hematologic diseases to examine the association with febrile neutropenia, and found that low IgA in saliva and high F.nucleatum, low diversity in fungal microbiota in the tongue coating were associated with the occurrence of febrile neutropenia. An anti-Fuso monoclonal antibody is being prepared for future detection and therapeutic application against Fuso.

Academic Significance and Societal Importance of the Research Achievements

Fusobacterium nucleatumは口腔内の嫌気性菌の一種として知られ、歯周病や大腸がんに関与している。しかし、全身化学療法によるそれらの細菌の影響などはほとんど検討されていない。Fusobacteriumの検出のための基礎検討や患者での口腔内環境と発熱性好中球減少症との関連を調査した。今後の治療応用を視野に入れた抗Fusobacterium抗体の作成などを行っており、今後の歯周病や大腸がん、がん化学療法の支持療法の進歩に対して意義ある研究と考える。