2022 Fiscal Year Final Research Report
Development a novel treatment for Crohns disease targeting intestinal epithelial cells
Project/Area Number |
21K15985
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Jikei University School of Medicine |
Principal Investigator |
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Project Period (FY) |
2021-04-01 – 2023-03-31
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Keywords | クローン病 / アミノ安息香酸 / 腸内細菌代謝産物 / 腸管上皮細胞 / 炎症性腸疾患 |
Outline of Final Research Achievements |
Caco2 cells were stimulated with a library of gut microbial metabolites and evaluated for the changes in the transepithelial electrical resistance (TEER). Among 119 metabolites, the highest elevation of TEER was obtained by stimulation with aminobenzoic acid. A 16S rRNA metagenomic analysis were performed on patient-derived stool samples and followed by a PICRUSt2-based functional prediction analysis. Functional prediction of intestinal microbiota demonstrated that patients with Crohn’s disease (CD) were significantly more enriched with the bacteria involved in the degradation of aminobenzoic acid than healthy controls. Liquid chromatography coupled with mass spectrometry (LC-MS) revealed a significantly reduced amount of fecal aminobenzoic acid in patients with CD than in the healthy controls. Rectal administration of aminobenzoic acid ameliorated dextran sulfate-induced colitis in mice with mitigated reduction of body weight loss and decreased intestinal weight/length ratio.
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Free Research Field |
炎症性腸疾患
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Academic Significance and Societal Importance of the Research Achievements |
クローン病患者の腸管における細菌代謝産物の構成変化については、短鎖脂肪酸やトリプトファン、胆汁酸などいくつかの報告が見られるが、アミノ安息香酸の減少については未だ報告はなく、クローン病の病態における役割も未だ不明である。本研究の成果によって、クローン病患者の腸管では、腸内細菌叢の機能変化に伴いアミノ安息香酸の分解が亢進しており、腸管上皮細胞間透過性の亢進を介して腸炎発症に寄与していることが示唆された。これらの結果は、クローン病の病態におけるアミノ安息香酸の役割を明らかとし、アミノ安息香酸を標的とした新たなクローン病治療の開発に有用と考える。
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