The Mechanisms of Glucose and Lipid Metabolism Regulation via Bile Acid Transporters

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08889
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kumamoto University
• Principal Investigator: Ishii Norio 熊本大学, 大学院生命科学研究部(医), 助教 (10599111)
• Co-Investigator(Kenkyū-buntansha): 瀬ノ口 隆文 熊本大学, 大学院生命科学研究部(医), 特任講師 (00530320) ; 近藤 龍也 熊本大学, 病院, 講師 (70398204)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胆汁酸トランスポーター / 腸内細菌叢 / 動脈硬化

Outline of Final Research Achievements

This study revealed that the inhibition of the ileal bile acid transporter (IBAT), which reabsorbs bile acids from the intestinal lumen, by the drug elobixibat, leads to quantitative changes in blood bile acid levels and quantitative/qualitative changes in bile acid profiles, improving glucose and lipid metabolism abnormalities via the bile acid signaling pathway. It has also been reported that the modulation of bile acid profiles by IBAT inhibition may interact with the gut microbiota. This clinically beneficial study demonstrated that changes in gut microbiota and bile acid profiles resulting from IBAT inhibition could be a new therapeutic target for glucose and lipid metabolism abnormalities.

Free Research Field

内科系臨床医学 脂質代謝異常 動脈硬化症

Academic Significance and Societal Importance of the Research Achievements

本研究は、IBAT阻害薬が糖代謝・脂質代謝異常の改善に有効であり、その作用機序を胆汁酸シグナル伝達経路を介して明らかにした点で学術的に極めて意義深い。また、IBAT阻害による腸内細菌叢と胆汁酸分画の変化が、新しい糖・脂質代謝異常治療のターゲットになる可能性が示せた点で医学的な学術的意義が大きい。IBAT阻害薬による治療法の確立は、安全かつ効果的な新しい治療法の開発に繋がり、患者のQOLの向上や医療費削減につながることが期待される。