Identification of gut microbiota involved in gut barrier dysfunction

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19420
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Tahara Satoko 筑波大学, 生存ダイナミクス研究センター, 講師 (20360589)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 腸管バリア / 腸内細菌

Outline of Final Research Achievements

Disruption of the intestinal barrier integrity is a leading cause of various gastrointestinal diseases, such as inflammatory bowel disease. An inhibitory immunoglobulin-like receptor, Allergin-1, is expressed on mast cells and dendritic cells and inhibits TLR-2 and TLR-4 signaling in these cells. Allergin-1-deficient mice exhibited more severe dextran sulfate sodium (DSS)-induced colitis than did wild-type mice. Allergin-1-deficient mice showed an enhanced intestinal permeability compared with WT mice even before DSS administration. The 16S rRNA gene sequencing analysis demonstrated that Bifidobacterium pseudolongum was the dominant bacterium in Allergin-1-deficient mice. These results demonstrated that Allergin-1 deficiency enhanced intestinal dysbiosis with expanded B. pseudolongum, which contributes to intestinal barrier dysfunction.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

腸管バリア機能の低下は、消化管疾患のみならず全身の疾患の発症に関わることから、腸管バリア機能低下に働く腸内細菌を明らかにし、この腸内細菌が腸管バリアの破綻に働く機序の一端を明らかにすることが出来れば、炎症性腸疾患、アレルギー、ガン、神経変性、老化などの病態の理解と治療法の開発に貢献することになり、科学的および社会的インパクトを有する創造性ある研究課題である.