Analysis of mucosa associated microbiota and fecal organic acids and development of new treatments for irritable bowel syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07903
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Shiotani Akiko 川崎医科大学, 医学部, 教授 (80275354)
• Co-Investigator(Kenkyū-buntansha): 内藤 裕二 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00305575) ; 井上 亮 摂南大学, 農学部, 教授 (70443926)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ドーパミンD2受容体

Outline of Final Research Achievements

The study examining the mucosal microbiota (MAM) of patients with irritable bowel syndrome (IBS) indicated that Butyrate-producing bacteria were decreased in the terminal ileum and Dorea was increase in the sigmoid colon. Differences were observed in bacterial composition ratio and functional analysis between diarrhea-type IBS and constipation-type IBS. In the chronic social defeat stress (cSDS) mouse model, significant infiltration of inflammatory cells and increased IL-6, and decreased MUC2, SERT, and HTR4 were observed compared to the control group. The expression level of dopamine D2 receptors in the pituitary gland was decreased in the cSDS mouse. We are planning comprehensive genetic analysis and fecal transplantation in mouse model.

Free Research Field

脳腸細菌叢相関

Academic Significance and Societal Importance of the Research Achievements

口腔からの通過菌を含む便の細菌叢をみるのではなく、宿主の免疫機構の調節あるいは脳腸相関に関わっていることが予想される粘膜細菌叢（MAM）を検討することは、臨床的意義を確認する上で重要である。回腸末端および大腸粘膜MAMの研究でIBS-CとIBS-DでMAMが異なることからサブタイプ別に病態解明を行い、治療戦略を検討する必要があると考えている。動物モデルの脳内の遺伝子発現におけるドーパミンの関与が示唆されたが、今後、網羅的に遺伝子解析を行い、糞便移植の効果を確認する予定である。脳腸細菌叢相関の観点からIBSの病態がさらに解明でき、IBS新規治療法の開発につながる可能性がある。