Maintenance of Intestinal Homeostasis by Symbiotic Bacteria Residing in Intestinal Immune-inducing Tissues and Its Association with Crohn's Disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K17686
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology); Immunology
• Research Institution: Waseda University (2018-2020); Chiba University (2017)
• Principal Investigator: Shibata Naoko 早稲田大学, ナノ・ライフ創新研究機構, 次席研究員(研究院講師) (60794542)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 腸管免疫 / 腸内細菌 / 樹状細胞

Outline of Final Research Achievements

The present study revealed that while lipopolysaccharide derived from Alcaligenes has low inflammatory activity, it promotes IgA production by B cells and efficiently induces antigen-specific immune responses when used as an adjuvant in vaccines. In addition, when Alcaligenes is overgrown, the form changes from rod-like to filamentous, and cytochrome c accumulated in the bacterial cells with the form change induces apoptosis of dendritic cells. In addition, regarding the effect of Alcaligenes on the onset and aggravation of Crohn's disease, a strong positive correlation was observed between serum Alcaligenes specific IgG antibody and Crohn's disease severity in small intestine colon type Crohn's disease. These results suggest that Alcaligenes specific antibody titer can be a new objective index for Crohn's disease.

Free Research Field

粘膜免疫学

Academic Significance and Societal Importance of the Research Achievements

腸管においてIgAは、病原性細菌・ウィルスの侵入阻害や、毒素の中和を行うことが知られており、本研究成果は、Alcaligenes菌が腸管免疫誘導組織であるパイエル板内に共生することで、IgA産生促進を介した生体防御に寄与していることを示唆している。また近年、腸内細菌叢や腸内細菌由来の代謝産物の異常が、関節リウマチの発症や自閉症、神経系の発達や機能に影響することが報告されており、本研究課題から得られる成果は、腸管にとどまらず、将来的には全身性の免疫疾患や炎症性疾患、神経疾患に対する新しい予防法および治療法へと波及する可能性を秘めている。