2024 Fiscal Year Final Research Report
Identification of intestinal microbiota that contribute to bile acid and lipid ester production and exploration of physiological mechanisms
| Project/Area Number |
22K08662
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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 54040:Metabolism and endocrinology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
成島 聖子 国立研究開発法人理化学研究所, 生命医科学研究センター, 上級研究員 (80578336)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Keywords | 便中胆汁酸 / 胆汁酸脂肪酸エステル / 腸内細菌叢 / GLP1 |
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| Outline of Final Research Achievements |
Fecal matter contains non-covalently bound bile acids (BAs) as well as saponifiable BAs, and it has been revealed that some of these are iso-type BAs (FA-isoBAs) esterified with fatty acids. Through the synthesis of analytical standards and LC/MS analysis, it was determined that FA-isoBAs are present in human feces from the age of 2 years onwards, with C16 and C18 chains predominating. Furthermore, one type of FA-isoBA, linoleoyl-isoLCA, was found to inhibit the production of inflammatory cytokines, while short-chain FA-isoBAs demonstrated a promotion of GLP-1 secretion and TGR5 receptor activity. Future studies will focus on elucidating their physiological effects and identifying the bacteria responsible for their production.
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| Free Research Field |
小児科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的意義は、これまで定量が困難であった糞便中の脂肪酸エステル型イソ胆汁酸（FA-isoBAs）を世界で初めて非鹸化のまま定量し、その存在実態と生理作用を明らかにした点にある。FA-isoBAsは年齢を問わず存在し、炎症性サイトカインの抑制、GLP-1分泌促進、TGR5活性化など多様な生理機能を有することが示された。また、FA-isoBAsが腸内細菌由来の内因性リガンドとして機能する可能性を初めて示し、腸内代謝物を基盤とした新たな疾患予防・治療法の開発につながる重要な知見を提供した。
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