Development of the new treatment applying microbiome analysis in the graft-versus-host disease related dry eye disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18394
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Keio University
• Principal Investigator: Shimizu Eisuke 慶應義塾大学, 医学部(信濃町), 特任講師 (10793812)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ドライアイ / 腸内細菌 / GVHD / 自己免疫 / 予防 / オーファン

Outline of Final Research Achievements

Hematopoietic stem cell transplantation is a curative therapy for hematologic malignant diseases, but can lead to complications of graft-versus-host disease (GVHD), which causes inflammation and fibrosis in organs throughout the body, especially in the eye, affecting the quality of daily life and life expectancy. Conventional GVHD therapies are mainly symptomatic treatments with strong side effects, such as steroids, and the social problems associated with treatment have become apparent. In this study, we focus on the autoimmune-like pathogenesis of GVHD and attempt to develop new treatment methods. Recent studies have revealed that intestinal bacteria are deeply involved in the immune system and play an important role in autoimmune diseases. We believe that conjunctival and intestinal bacteria are highly associated with GVHD-related dry eye and propose a novel approach to treat GVHD by immunosuppression through changes in the bacterial flora, and also to prevent GVHD.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、病態に基づいた新規治療法の開発に注目し、その学術的な特色を発揮しています。特に、移植片対宿主病（GVHD）の合併症に対する治療という未開拓の領域において、病態に直接作用する治療法の開発を試みています。GVHDモデルにおいて、GM（グラム陰性菌）の経口投与によりGVHDの表現型が改善されることが確認されました。これは、新規かつ臨床的に有用な治療戦略として認識されており、2022年度にはそのエビデンスが公表されました。新規治療法の開発は、副作用の少ない病態に基づいた治療法を提供し、学術的にも貢献する可能性があると考えられます。