Exploring novel therapies on the basis of pathophysiological commonality between irritable bowel syndrome and metabolic syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07896
• 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: Asahikawa Medical College
• Principal Investigator: Nozu Tsukasa 旭川医科大学, 医学部, 教授 (30312367)
• Co-Investigator(Kenkyū-buntansha): 奥村 利勝 旭川医科大学, 医学部, 教授 (60281903)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 過敏性腸症候群 / 腸管感覚 / 腸管バリアー / メタボリックシンドローム

Outline of Final Research Achievements

Majority of the patients with irritable bowel syndrome (IBS) are known to display visceral hypersensitivity and increased gut permeability. In the present study, we demonstrated that these changes were mediated via CRF, TLR4 and proinflammatory cytokine signaling in rat IBS model. Incidentally, CRF, TLR4 and proinflammatory cytokine signaling have been also reported to be involved in the pathophysiology of metabolic syndrome. We also showed that the drugs used in metabolic syndrome improved these gastrointestinal changes in IBS model, possibly by the suppression of proinflammatory cytokine signaling. These results suggest that IBS and metabolic syndrome may have a similar pathophysiology, which may be a hint for the development of novel therapy of IBS.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

IBSはQOLを著しく低下させることより欠勤や不登校を高率に生じさせ，社会的にも大きな問題となっている．IBSの治療は多くが対症療法であり，治療選択肢は乏しい．今回の研究により，メタボリックシンドロームとIBSには共通の機序が存在することが明らかとなった．さらにこの知見から，メタボリックシンドロームの治療薬が，IBSでも効果を発揮するのではないかという仮説を建て，実際その仮説が正しいことを明らかにした．これらの結果は，既存のメタボリックシンドローム治療薬が，IBS患者でも効果があることを示唆し，臨床応用のハードルが低い，既存治療薬の適応拡大という新しいIBSの治療アプローチをを提案できた．