Mucosa-associated microbiota and bacteriophage in the pathophysiology of irritable bowel syndrome (IBS)

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08020
• 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), 准教授 (00305575)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 粘膜細菌叢 / 過敏性腸症候群 / 酪酸産生菌

Outline of Final Research Achievements

The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C). Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum were significantly different among the 3 groups. In addition, the proportion of genes at the functional level differed between the IBS-D group and the IBS-C group. Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation.

Free Research Field

消化管内科

Academic Significance and Societal Importance of the Research Achievements

本研究により、酪酸産生菌が過敏性腸症候群（IBS）で有意に少く、便秘型IBS-Cと下痢型IBS-D間で粘膜細菌叢(MAM)の細菌構成比および機能解析に差を認めることを報告した。酪酸は、腸管上皮のアポトーシス抑制やバリア強化に関わり、過剰な免疫応答を抑制し、腸管免疫系の形成に重要な役割を果たすことが報告されている。しかしIBSサブタイプ別にMAMに注目し、検討した報告はほとんどなく、細菌代謝産物を治療に応用した報告はない。MAM代謝産物と病態あるいは重症度との関連性をさらに確認し、それらの効果を動物モデルで確認することにより、IBS新規治療法の開発につながる可能性がある。