| Project/Area Number |
15K11084
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Showa University |
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Principal Investigator |
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| Research Collaborator |
Kuwata Hirotaka
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 食物アレルギー / 口腔内細菌叢 / 腸内細菌 / IL-33 / Citrobacter / 腸内細菌叢 / IgA / Th17 / 過酸化水素産生細菌 / ディスバイオーシス / 常在細菌叢 / 免疫応答 / 免疫 |
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| Outline of Final Research Achievements |
Food allergy is a life-threatening response to specific foods, and microbiota imbalance in gut is considered a cause of this disease. In this study, we analyzed effects of gut and oral microbiota on development of food allergy. A murine model of food allergy was established via ovalbumin (OVA) injection in BALB/c mice. Viable fecal bacteria in feces of the allergic mice were identified using MALDI-TOF MS. Citrobacter sp. increased in the feces of allergic mice and induced il33, known as a cytokine that stimulates Th2 responses, expression in colon 26, mouse intestinal epithelial cells. Orally administered Citrobacter sp. exacerbated systemic allergic symptoms and reduced intestinal Th17 cells. Salivary IgA and IgA-bound oral bacteria increased in the allergic mice. From the above, food allergy affects constitution of both gut and oral microbiota. Citrobacter sp. aggravated allergic symptoms by inducing IL-33 release from intestinal epithelial cells.
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| Academic Significance and Societal Importance of the Research Achievements |
口腔内細菌叢を構成する細菌は、全身疾患にも影響を及ぼすことは報告されているが、その詳細は未だ不明である。本研究では、食物アレルギーで増加する腸内細菌とそれに対する免疫応答が、口腔内細菌叢の構成を変化させることを示した。この研究成果によって、口腔内細菌叢と食物アレルギー症状の関連性が初めて明らかになった。近年、食物アレルギーの患者は増加傾向にあるが、その有効な治療法は未だ確立されていない。本研究の成果から、食物アレルギーの治療だけでなく予防においても口腔内細菌を活用できる可能性が示された。さらにこの成果から、他の自己免疫疾患の治療と予防にも口腔内細菌を活用できる可能性が示唆された。
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