Understanding mechanisms of disease development via disrupted Paneth cell development involving maturation and formation of intestinal microbiota

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H04098
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Hokkaido University
• Principal Investigator: Nakamura Kiminori 北海道大学, 先端生命科学研究院, 教授 (80381276)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Paneth細胞 / αディフェンシン / 腸内細菌 / 共生 / 先制医療

Outline of Final Research Achievements

The living environment during pregnancy is increasingly known to influence the child's future health and disease risk (DOHaD). The involvement of the maternal gut microbiota, which is influenced by diet, as one of the environmental factors inducing DOHaD has increased concern, but the underlying mechanisms are unknown. This study showed that gut microbiota disruption via decreased α-defensin due to maternal high-fat diet intake prevents maturation of the child's gut microbiota by inducing abnormal Paneth cell development due to epigenetic modifications during the embryonic period. These findings contribute to the establishment of novel disease prevention methods that target α-defensin during the maternal gestation period to reduce the risk of developing a child's disease.

Free Research Field

腸管粘膜免疫

Academic Significance and Societal Importance of the Research Achievements

本研究は、いまだ十分に理解されていない腸内細菌叢形成機序の解明において、宿主因子であるPaneth細胞・α-defensinが個人の多様な腸内細菌叢の成熟・形成に大きく関与するという独自性の高い発想を基とした仮説を証明することにより、自然免疫による細菌叢との共生機構を標的とした疾患の予防・治療に直結する独創的で画期的な先制医療シーズを創出する基盤を構築したことから、学術的および社会的な要請において大きく意義がある。