Establishment of new treatment for chronic pulmonary aspergillosis with modulating microbiota of gut

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09936
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nagasaki University
• Principal Investigator: IZUMIKAWA Koichi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (20404212)
• Co-Investigator(Kenkyū-buntansha): 田代 将人 長崎大学, 医歯薬学総合研究科(医学系), 助教 (20713457)
• Research Collaborator: NAKANO Yuichiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アスペルギルス

Outline of Final Research Achievements

The aim of this study is to reveal the relation between the pathogenesis of chronic pulmonary aspergillosis and microbiota of gut and/or respiratory system. Chronic aspergillus infection with anti-aspergillus antibody production mouse model was established in first two years. The microbiota of this mouse model was modified with cefoperazone/sulbactam (C/S) contained drinking water and explore the influences to anti-aspergillus antibody production in C/S treated mice. The microbiota of mice treated with C/S was dramatically changed into only kind of enterobacteriaceae family, though varieties of enterobacteriaceae bacteria were proved in C/S un-treated mice group. The production of anti-aspergillus antibody was reduced in C/S treated mice with aspergillus challenged compared to those of C/S un-treated mice group. This result indicated that microbiota of gut influences the immunological effect against Aspergillus infection.

Free Research Field

感染症学

Academic Significance and Societal Importance of the Research Achievements

慢性肺アスペルギルス症は、難治性で予後不良な真菌症であり、おもに結核の治療後に罹患する。先進国でも結核の中蔓延国である我が国においては、潜在的に多くの患者が存在している。抗真菌薬が奏功しない例も多く、抗真菌薬に依存しない治療法の開発がもとめられる。腸内細菌叢はヒトの免疫能に影響を及ぼすと言われているが、今回のマウスを用いた動物実験結果から、アスペルギルス症において腸内細菌叢が、アスペルギルスに対する感染防御能を変化させるために重要な役割をしている可能性があることが証明された。腸内細菌叢をコントロールし、アスペルギルス症に対する免疫能を賦活化させる新しい治療につながる可能性を示した。