Elucidation of the Mechanism of the Central Nervous System Regulation of Intestinal Barrier Function and Its Application to the Treatment of Leaky Gut-related Disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07883
• 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: Ishioh Masatomo 旭川医科大学, 大学病院 総合診療部, 医員 (50869211)
• Co-Investigator(Kenkyū-buntansha): 野津 司 旭川医科大学, 医学部, 教授 (30312367)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Leaky gut / Brain / Adenosine A2B / Ghrelin / Orexin / Butyrate / IBS

Outline of Final Research Achievements

We revealed that the central nervous system regulation of intestinal barrier function by brain ghrelin does not involve brain opioid, dopamine, or cannabinoid signals, but rather, it involves adenosine A2B signaling.　Furthermore, we found that the activation of adenosine A2B signaling in the brain also regulates intestinal barrier function, and this mechanism involves the activation of the vagus nerve system.

Free Research Field

神経消化器病

Academic Significance and Societal Importance of the Research Achievements

脳内ghrelinに加え, 脳内adenosine A2Bシグナルが, leaky gutを改善させることを見出した. leaky gut関連疾患である過敏性腸症候群(IBS)は, 抑うつ・不安などの精神症状を高率に合併し, 病態を増悪させる. ghrelinおよび本研究で見出したadenosine A2Bシグナルは抗精神作用を有することも報告されており, これらの中枢神経系による腸管バリア機能制御機序の解明は, IBSの画期的な創薬研究につながると考える.