2023 Fiscal Year Final Research Report

The Optimization of Oral Lactobacillus Oligodeoxynucleotide Microparticles and the Elucidation of Immune Regulation Mechanisms via Intestinal Epithelium

Research Project

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Project/Area Number	20H03125
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 42010:Animal production science-related
Research Institution	Shinshu University
Principal Investigator	Shimosato Takeshi 信州大学, 学術研究院農学系, 教授 (00467200)
Co-Investigator(Kenkyū-buntansha)	佐藤隆信州大学, 先鋭領域融合研究群バイオメディカル研究所, 特任教授 (70510436) 重盛駿信州大学, 先鋭領域融合研究群バイオメディカル研究所, 助教(特定雇用) (90803487) 荻田佑信州大学, 学術研究院農学系, 助教 (50738010)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	乳酸菌 / オリゴDNA / 微粒子 / 腸管
Outline of Final Research Achievements	Previously, we developed acid-resistant particles (ODNcap) as an oral delivery device for ODNs. When taken up by intestinal mucosal cells, these edible ODNs retained their immunomodulatory activity. The ability to produce particles containing immunomodulatory ODNs opens the possibility of using ODNcaps in mouse disease model studies. This study showed that free feeding of an ODNcap-feed prophylactically attenuates allergic airway inflammation, hyperresponsiveness, and goblet cell hyperplasia in an asthma model. Using transcriptomics-driven approaches, we demonstrated that injury of pulmonary vein cardiomyocytes accompanies an allergen inhalation challenge but is inhibited by ODNcap feeding. We also showed the participation of an airway antimicrobial peptide and gut microbiota in the ODNcap-mediated effects. This approach may lead to developing novel foods and feeds that will prevent or suppress many types of infectious, allergic, inflammatory, and autoimmune diseases.
Free Research Field	動物生産科学
Academic Significance and Societal Importance of the Research Achievements	本研究により、アレルギー性気管支炎の病態は、肺静脈心筋細胞の傷害を伴うことを発見し、乳酸菌オリゴDNA微粒子（ODNcap）の摂取は、この傷害を軽減することを見出した。これらの結果は、ODNcapが腸管を起点とする腸肺相関に関与していることを示唆している。今後は、ODNcapの有効性、安全性、治療可能性、および作用機序を検証するためのさらなる研究が必要である。乳酸菌オリゴDNAを有効成分とする気道炎症に対する予防薬や、機能性素材（食品素材や核酸医薬）の開発に役立つ知見が得られた。