Basis for the research of identification of gut microbiota in pancreatic cancer and clinical application

• Project/Area Number: 18K15800
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Satoshi Shiba 国立研究開発法人国立がん研究センター, 研究所, 研究員 (00797003)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マイクロバイオーム / メタボローム / 腸内細菌 / 腸内代謝物質 / がん / 腸内環境 / メタゲノム / 腸内細菌叢 / 膵がん / 大腸がん / S-1

Outline of Final Research Achievements

We have established a basis for the research of gut microenvironment in cancer patients, and reported a novel research that specific gut microbiota exist in individuals with advanced colorectal cancer regardless of race, collaborating with research groups in Italy and Germany. Furthermore, we have revealed that unique gut microenvironment (specific microbiota and metabolite) are found in patients with multiple colon polyps or intramucosal carcinoma for the first time in the world. At the same time, we also investigated how gastric or colorectal surgery affect gut environment, and summarized the change of gut microenvironment after surgery and reported a novel discovery in international journals.
In the future, using collected samples from patients with pancreatic cancer, we are going to elucidate the gut microenvironment in pancreatic cancer comparing with the previous report, and then promote clinical application based on our past achievements in parallel.

Academic Significance and Societal Importance of the Research Achievements

本研究を通して、健康な方や疾患を有する方の便サンプルを用いて腸内細菌叢及び腸内代謝物質を解析することで、疾患に特有の腸内環境を明らかにし、臨床情報との関連を結び付ける研究基盤を確立した。今後は、特定の疾患や治療に関連する腸内環境を解明し、早期診断や治療に役立つバイオマーカーの開発、さらに、腸内細菌や腸内代謝物質を利用した新たな創薬への展開も期待される。

Research Products

• [Journal Article] Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits. (2022)
  • Author(s): Shiroma H, Shiba S, Erawijantari PP, Takamaru H, Yamada M, Sakamoto T, Kanemitsu Y, Mizutani S, Soga T, Saito Y, Shibata T, Fukuda S, Yachida S, Yamada T.
  • Journal Title: mSystems Volume: 7 Issue: 2
  • DOI: 10.1128/msystems.00018-22
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER (JCOG1804E) (2020)
  • Author(s): Yamamoto Shun、Kato Ken、Daiko Hiroyuki、Kojima Takashi、Hara Hiroki、Abe Tetsuya、Tsubosa Yasuhiro、Nagashima Kengo、Aoki Kazunori、Mizoguchi Yukihiro、Kitano Shigehisa、Yachida Shinichi、Shiba Satoshi、Kitagawa Yuko
  • Journal Title: Future Oncology Volume: 16 Issue: 19 Pages: 1351-1357
  • DOI: 10.2217/fon-2020-0189
  • Peer Reviewed / Open Access
• [Journal Article] Influence of gastrectomy for gastric cancer treatment on faecal microbiome and metabolome profiles (2020)
  • Author(s): Erawijantari Pande Putu、Mizutani Sayaka、Shiroma Hirotsugu、Shiba Satoshi、Nakajima Takeshi、Sakamoto Taku、Saito Yutaka、Fukuda Shinji、Yachida Shinichi、Yamada Takuji
  • Journal Title: Gut Volume: - Issue: 8 Pages: 1-12
  • DOI: 10.1136/gutjnl-2019-319188
  • Peer Reviewed / Open Access
• [Journal Article] Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer (2019)
  • Author(s): Wirbel Jakob, Shiba Satoshi, et al.
  • Journal Title: Nature Medicine Volume: 25 Issue: 4 Pages: 679-689
  • DOI: 10.1038/s41591-019-0406-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation (2019)
  • Author(s): Andrew Maltez Thomas, Paolo Manghi, Francesco Asnicar, Edoardo Pasolli, Federica Armanini, Moreno Zolfo, Francesco Beghini, Serena Manara, Nicolai Karcher, Chiara Pozzi, Sara Gandini, Davide Serrano, Sonia Tarallo, Antonio Francavilla, Gaetano Gallo, 他25名
  • Journal Title: Nature medicine Volume: 25 Issue: 4 Pages: 667-678
  • DOI: 10.1038/s41591-019-0405-7
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer (2019)
  • Author(s): Yachida Shinichi、Mizutani Sayaka、Shiroma Hirotsugu、Shiba Satoshi、Nakajima Takeshi、Sakamoto Taku、Saito Yutaka、Fukuda Shinji、Shibata Tatsuhiro、Yamada Takuji
  • Journal Title: Nature Medicine Volume: 25 Issue: 6 Pages: 968-976
  • DOI: 10.1038/s41591-019-0458-7
  • Peer Reviewed / Open Access
• [Presentation] 便メタゲノムおよびメタボローム解析による大腸多段階発癌における腸内微生物叢・微小環境の特徴と可能性 (2020)
  • Author(s): 高丸博之, 柴 知史, 坂本 琢, 山田真善, 斎藤 豊
  • Organizer: 2020年度日本消化器関連学会（JDDW 2020）
• [Presentation] FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF therapy for locally advanced esophageal carcinoma (JCOG1804E) - The short-term results of cohort A and B. (2020)
  • Author(s): Yamamoto S, Kato K, Daiko H, Kojima T, Hara H, Abe T, Tsubosa Y, Kawakubo H, Fujita T, Fukuda T, Kadowaki S, Tsushima T, Hamamoto Y, Nagashima K, Aoki K, Mizoguchi Y, Kitano S, Yachida S, Shiba S, Kitagawa Y
  • Organizer: 2021 Gastrointestinal Cancers Symposium.
  • Int'l Joint Research