| Project/Area Number |
18K19721
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
Nakayama Toru 東北大学, 工学研究科, 教授 (80268523)
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| Co-Investigator(Kenkyū-buntansha) |
大平 英夫 神戸学院大学, 栄養学部, 准教授 (40351762)
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| Project Period (FY) |
2018-06-29 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アルコール / 飲酒習慣 / 酸化ストレス / 終末糖化産物 / エタノール / 大腸がん / 腸内細菌 / 慢性投与 / アセトアルデヒド |
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| Outline of Final Research Achievements |
Chronic oral administration of ethanol in mice resulted in the elevation of colonic levels of oxidative stress markers, and this was consistently accompanied by elevated levels of inflammation-associated markers and a decreased level of regulatory T cells. It also resulted in an alteration of mouse fecal microbiota structures, reminiscent of the alterations observed in human inflammatory bowel disease, and this appeared to be consistent with the proposed sustained generation of oxidative stress in the colonic environment during chronic ethanol consumption. Chronic ethanol administration results in elevated levels of advance glycation end products and their receptors in the colonic tissues in mice is also shown. Thus, enhancement of this pathway likely exacerbates the ethanol-induced inflammatory states of colonic tissues and might at least partly contribute to the pathogenesis of chronic colitis, ethanol-related colorectal cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
疫学的研究により，習慣的な多量飲酒が大腸がん発症リスクを増大させることが分かっているが，そのメカニズムについては未だ不明な点が多い．本研究の成果から，習慣的多量飲酒が結腸内にて酸化ストレス増加を慢性的に誘導し，腸内細菌叢構造を変化させることが示唆された．また，これらには結腸組織への終末糖化産物蓄積の寄与も関わっていると推察された．抗酸化作用を有する食品成分を毎日摂取するような食習慣をとることによって，習慣的多量飲酒に起因する慢性大腸炎・がん発症の予防が可能となるかもしれない．
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