| Project/Area Number |
18K11094
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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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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
柳川 徹 筑波大学, 医学医療系, 教授 (10312852)
蕨 栄治 筑波大学, 医学医療系, 講師 (70396612)
正田 純一 筑波大学, 医学医療系, 教授 (90241827)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | NASH / 歯周病 / LPS / メタゲノム解析 / 遺伝子改変マウス / 肝癌 / 歯周病菌 / 転写因子Nrf2 / ゲノム解析 / 脂肪性肝炎 / 運動療法 / 腸内細菌叢 / Kupffer細胞 / 肝星細胞 |
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| Outline of Final Research Achievements |
Salivary component analysis was performed for obese middle-aged men with NAFLD and periodontal disease. Diversity analysis of oral bacterial flora revealed a decreased alpha- and beta-diversity. In addition, higher salivary immunoglobulin A, cytokine, bacterial LPS, and lactoferrin concentrations were observed. However, an exercise regimen improved the oral environment of NAFLD patients by increasing the diversity of the oral microflora.
p62/Sqstm1-knockout (p62-KO) mice alongside hyperphagia-induced obesity develop phenotypes that are similar to clinical features of human NASH. The phagocytic capacity of Kupffer cells (KCs) were lower in the p62-KO group than in the WT group, but the capacity and LPS clearance increased with long-term exercise. It is suggested that long-term exercise reduces a flux of LPS from oral and intestinal bacteria into the liver and thereby prevents the development of NASH by ameliorating hepatic inflammation and fibrogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
運動が口腔内環境に及ぼす効果として，運動介入試験より，唾液中の炎症に関わる物質の濃度減少，口腔内細菌の種多様性の増大を明らかにした．運動が歯周病の改善をもたらすことのメカニズムが解明された．また，肥満マウスを用いた動物実験において，運動実践が腸内細菌叢や口腔内細菌叢に影響を与えて，LPSの暴露により誘導されるNASH肝病変の発症を予防することも明らかとなった．肥満者，糖尿病，高齢者など歯周病の高リスクグループに対する健康管理の一環として，運動実践の重要性がより明確になった．
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