Metagenomic analysis of familial adenomatous polyposis and its implications for understanding the pathogenesis of colorectal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03662
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka University
• Principal Investigator: Yachida Shinichi 大阪大学, 大学院医学系研究科, 教授 (20359920)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腸内細菌 / 大腸癌

Outline of Final Research Achievements

Stool samples and lifestyle questionnaires were obtained from unoperated patients diagnosed with familial adenomatous polyposis. Frozen stool samples were subjected to shotgun metagenomic and metabolomic analyses in order to compare intestinal bacteria and metabolites associated with patients diagnosed with FAP and age- and sex-matched healthy controls. Subsequently, individual variances among FAP patients were categorized using Dirichlet multinomial mixtures (DMM) modeling. This led to the identification of a specific group with corresponding DMMs when matched with FAP grade, encompassing factors such as maximum tumor diameter, number of polyps, histologic grade, and presence of dense lesions.

Free Research Field

ゲノム医科学

Academic Significance and Societal Importance of the Research Achievements

大腸癌におけるFirst hitとなる遺伝子異常はAPC遺伝子の変異である。FAP患者はこのAPC遺伝子の生殖細胞系変異を有している。散発性大腸癌の自然史は約20年であることから、大腸癌の原因となる環境因子（腸内細菌など）を特定することは困難である。一方、FAP患者においては発癌までの期間が短いため、FAP患者における腸内環境の変化を解析することで、短期間で効率的に発癌における環境因子の影響を解明することが可能となる。