Mechanism of progression of dementia and sarcopenia through gut-brain-muscle linkage mediated by monocytes and microglia

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K19769
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Department of Clinical Research, National Hospital Organization Kyoto Medical Center
• Principal Investigator: Satoh-Asahara Noriko (佐藤哲子) 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究部長 (80373512)
• Co-Investigator(Kenkyū-buntansha): 菅波 孝祥 名古屋大学, 環境医学研究所, 教授 (50343752) ; 小谷 和彦 自治医科大学, 医学部, 教授 (60335510)
• Project Period (FY): 2018-06-29 – 2022-03-31
• Keywords: 単級極性 / ミクログリア / 腸内細菌叢 / 認知機能 / サルコペニア / 臓器連関 / 腸脳筋連関

Outline of Final Research Achievements

We recognized the deterioration of intestinal microflora function and chronic inflammation, which is a risk for dementia and sarcopenia, in diabetic patients. In this study, we examined the pathogenesis of dementia and sarcopenia (gut-brain-muscle linkage) due to pathological interactions with the brain and muscle starting from the deterioration of the intestinal environment. In particular, we focused on function of monocyte/macrophage/microglia (M1/M2 polarity, TREM2) as a player of the pathological linkage, and found that serum sTREM2 is a predictive indicator of dementia and brain inflammation in the general population, diabetes mellitus and obese diabetic model mice. We generated TREM2-deficient mice to elucidate the mechanism of progression. In addition, we have clarified the effects of administration of diabetic drugs and flavonoids on the gut-brain-muscle interaction to establish optimal prophylaxis.

Free Research Field

内分泌・代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究では糖尿病・肥満患者において慢性炎症、特に免疫担当細胞である単球・マクロファージ極性（M1/M極性・TREM2発現）異常を基盤に病的な腸-脳-筋連関が生じ、認知症やサルコペニアが発症・進展する可能性が示唆された。本研究の成果は、加齢・代謝性疾患にて悪化する腸-脳-筋連関の包括的な予知バイオマーカーや予防法の確立に繋がり、超高齢社会の本邦で増加し問題となる生活習慣病に伴う認知症・サルコペニアに対する包括的・革新的先制医療の実現や健康寿命延伸に寄与でき、本邦の医療と福祉に多大な波及効果と貢献が期待できる。