Promotion of personalized medicine for lifestyle-related diseases by revealing bile acids, microbiota and cell signaling interaction

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05292
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: WATANABE Mitsuhiro 慶應義塾大学, 政策・メディア研究科(藤沢), 教授 (10450842)
• Co-Investigator(Kenkyū-buntansha): 横山 葉子 慶應義塾大学, 政策・メディア研究科(藤沢), 特任助教 (10617244) ; 滝川 一 帝京大学, 医学部, 教授 (70197226) ; 松崎 靖司 東京医科大学, 医学部, 教授 (50209532)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胆汁酸 / 腸内細菌 / 糖尿病 / 肥満 / 消化器 / 代謝

Outline of Final Research Achievements

In recent years, it has been clarified that bile acids not only promote digestion and absorption of lipids, but also regulate metabolism as signal molecules. Bile acids were administered to two strains of mice with different bile acids responsiveness, with and without antibiotics. Multi-omics analysis such as bile acids composition, DNA microarray, microbiota analysis were performed. In addition to the difference in bile acids, lipid and cholesterol metabolism due to genetic background, the change in bile acid composition metabolized by microbiota was different depending on the presence or absence of obesity / diabetes suppression effect by bile acid in two strain mice. It turned out that they interact and affect intricately.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

２系統マウスを用いた研究はR.Khan らによって精力的に行われ、PKC-δなど糖尿病を誘発する原因遺伝子の同定が行われてきたが、根本的なメカニズム解明には至っていない。しかしながら、我々が見出した2 系統マウスにおける胆汁酸応答性による生活習慣病発症差異に加えて、胆汁酸代謝-腸内細菌-宿主遺伝的背景という新たな視点から本研究を推進することで、人の個人的発症差異が存在する生活習慣病誘発の根本的な原因を抽出することができ、全く新しいストラテジーに基づく個別化予防・治療法の提唱に結びつけることができると考えている。