Analysis of autoimmune dysregulation caused by changes in intestinal microbiota due to environmental factors

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Juntendo University
• Principal Investigator: Hayakawa Kunihiro 順天堂大学, 大学院医学研究科, 准教授 (00573007)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 自己免疫疾患 / 腸内細菌叢 / 環境要因 / 免疫寛容

Outline of Final Research Achievements

This study investigated whether chronic activation of TLR7 signaling alters the intestinal environment and contributes to subsequent autoimmune responses. Changes in the intestinal microbiota were observed one week after the initiation of TLR7 agonist stimulation, peaking at two weeks. A metagenomic analysis was attempted, but the changes were dependent on the individual prior to stimulation, thus the details could not be elucidated specific bacterial species changes. Furthermore, we attempted to reduce the intestinal microbiota by administering antibiotics and protect the intestinal epithelial barrier, and examined the impact on autoantibody production. However, no changes were observed in autoantibody production. These results suggest that TLR7 signal activation alters the intestinal microbiota, but it is not yet clear whether this change is directly associated with autoimmune diseases.

Free Research Field

医歯薬科学・基礎医学・実験病理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、慢性的なTLR7シグナル活性化が腸内細菌叢を変化させることを明らかにし、ウイルス感染症等が腸内細菌叢を変化させることが示唆された。さらに、その変化が自己免疫疾患と関連しているかを検証したが、その関連性は明確ではなかった。しかし、この点を解明することは、自己免疫疾患の発症メカニズムを理解し、治療法を開発する上で重要である。また、腸内細菌叢の変化は個体によって異なるため、腸内細菌叢をターゲットとした治療戦略は、個々の患者に合わせた個別化医療として検討する必要がある。