Dysregulation of intestinal homeostasis by ammonia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H04052
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Hiroshima University
• Principal Investigator: Suzuki Takuya 広島大学, 統合生命科学研究科(生), 教授 (30526695)
• Co-Investigator(Kenkyū-buntansha): 井上 亮 摂南大学, 農学部, 教授 (70443926)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腸管バリア / アンモニア / タイトジャンクション

Outline of Final Research Achievements

The intestinal tract is the front line of biological defense (barrier) that prevents the entry of large numbers of foreign substances into the intestine. When the intestinal barrier is out of control, it leads to various inflammation-based diseases. The purpose of this study was to clarify the mechanism of disruption of intestinal homeostasis by ammonia, a major metabolite of intestinal bacteria. A series of studies revealed that ammonia accumulated abnormally in the intestinal tract damages tight junctions, the main structure of the intestinal barrier, and that this effect is caused by ammonia damaging the mitochondrial function of intestinal epithelial cells and causing oxidative stress. The results of this study demonstrate a new mechanism of intestinal barrier regulation.

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Free Research Field

食品科学

Academic Significance and Societal Importance of the Research Achievements

腸管バリアの損傷は、炎症性腸疾患だけでなく、代謝性疾患、腎臓病、自閉症スペクトラムなど、様々な疾患の発症や進展に関わることが明らかになり、新たな治療ターゲットとしても注目されてきている。本研究は、アンモニアが腸管バリアのネガティブレギュレータであることを見出し、その作用機序を明らかにした。広く人の研究に貢献しうることが考えられる。