A novel therapeutic strategy for pancreatic and biliary tract cancer by targeting the intestinal microbiota for anti-tumor immune activation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02996
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Tohoku University
• Principal Investigator: UNNO MICHIAKI 東北大学, 医学系研究科, 教授 (70282043)
• Co-Investigator(Kenkyū-buntansha): 古川 徹 東北大学, 医学系研究科, 教授 (30282122) ; 青木 修一 東北大学, 大学病院, 助教 (30844451) ; 阿部 高明 東北大学, 医工学研究科, 教授 (80292209)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膵癌 / 胆道癌 / 腸内細菌 / 術前治療

Outline of Final Research Achievements

Gut microbiota is considerably associated with human health, disease status, and sensitivity to oncological treatments. However, in pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), the association of gut microbiota has not been clarified. Here, we aimed to delineate gut microbiota characteristics in patients with PDAC and CCA and prove their implications in chemotherapeutic sensitivity. Fecal samples were obtained and profiling was performed via 16S rRNA. The microbiota of PDAC and CCA patients exhibited a unique, significantly less diverse than controls. Proteobacteria were predominant, whereas Actinobacteria were notably diminished, particularly in PDAC. In the efficacy to chemotherapy in PDAC, the specific bacterial genera and species, were identified as potential biomarkers for chemotherapeutic resistance. In conclusion, PDAC and CCA patients had decreased diversity of gut microbiota and shows a potential biomarker of microbiota for resistance to chemotherapy.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

腸内細菌は100兆個を超える細菌により形成され、ヒトの生理機能や感染防御に重要な役割を果たしている。固形癌の中で最も予後が悪い膵癌、胆道癌の腸内細菌叢解析を行ったところ、膵癌胆道癌には特有の細菌叢組成を認め、抗がん剤治療の効果と関係する数種類の菌株を同定した。これらの結果は、膵癌胆道癌の発癌予防や新しい薬剤の開発、腸内細菌叢をもとにした個別化した治療体系の構築につながる可能性がある。