Investigation of the influence of fatty acid metabolites on the pathogenesis of IBD.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22762
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: OKABE MAKOTO 京都大学, 医学研究科, 医員 (80886953)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: ketoC / IBD / 腸内細菌

Outline of Final Research Achievements

Using RNA-seq, we confirmed that ketoC exhibits anti-inflammatory effects in mouse bone marrow-derived macrophages. We found that ketoC is involved in the suppression of TNF signaling and anti-inflammatory signaling.
We also confirmed that intravenous administration of linoleic acid and ketoC, a linoleic acid metabolite, both showed anti-inflammatory effects in a mouse model of IBD (DSS enteritis mice). Furthermore, when the same experiment was conducted using a sterile-like model mouse, ketoC had an intestinal inflammation inhibitory effect, but linoleic acid did not show an intestinal inflammation inhibitory effect. Therefore, ketoC, which is produced by the metabolism of linoleic acid by intestinal bacteria, was considered to be effective in suppressing intestinal inflammation. Therefore, ketoC can be used for the treatment of IBD.

Free Research Field

炎症性腸疾患

Academic Significance and Societal Importance of the Research Achievements

本邦におけるIBD患者数は劇的に増加しており、生物学的製剤を含めた新規薬剤が多く開発されている。しかしながら、いずれの薬剤も副作用や高額な医療費を要することから安全・安価な薬剤の登場が期待される。本研究では、必須脂肪酸であるリノール酸が腸内細菌で代謝されてketoCに腸炎抑制効果があることが見出された。ketoC自体は健常人の腸管内にも存在している。そのためIBD患者に対するketoCの腸炎抑制効果が確認されれば、非常に安全性の高い新規薬剤として社会的意義は大きいと思われる。