Identification of gut microbiota that regulates the development of chronic pancreatitis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17506
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kindai University
• Principal Investigator: Minaga Kosuke 近畿大学, 大学病院, 助教 (30793814)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 慢性膵炎 / 腸内細菌 / 自然免疫反応

Outline of Final Research Achievements

Although bacterial translocation to systemic organs is sometimes observed in patients with pancreatitis, the gut microbiota accounting for the development of chronic pancreatitis has not been identified. In this study, we aimed to identify the gut microbiota that regulates the development of chronic pancreatitis and analyze its functions. According to the fecal microbiota analysis in experimental chronic pancreatitis, a disappearance of Akkermansia muciniphila (A. muciniphila) from the feces contributes to the development of chronic pancreatitis, whereas pancreatic enzyme replacement therapy may prevent the development of chronic pancreatitis by enhancing the colonization of A. muciniphila in the gastrointestinal tract. Increased colonization of A. muciniphila may prevent chronic pancreatitis by suppression of the infiltration of immune cells into the pancreas and by suppression of type I IFN and IL-33 productions by pancreatic acinar cells.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

慢性膵炎は飲酒過剰を背景に発症する膵臓の慢性炎症性疾患であり、膵内・外分泌機能が障害される結果、糖尿病や難治性の疼痛・下痢などが出現する。また、慢性膵炎は膵癌発症の最大の危険因子である。しかしながら、慢性膵炎の病態生理は十分に解明されておらず、病態生理に基づいた根治療法は開発されていない。本研究において、腸内細菌叢解析の結果、Akkermansia muciniphilaが慢性膵炎の発症抑制に機能する腸内細菌であることが示唆された。本菌は肥満や脂肪肝などを抑制することが報告されているが、慢性膵炎や予後不良な膵癌の発症予防にも有効である可能性があり、新たな治療法の開発につながる可能性がある。