Elucidation of the mechanisms of metabolic adaptation in gut microbial ecosystem

• Project Area: Transomic Analysis of Metabolic Adaptation
• Project/Area Number: 18H04805
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Research Institution: Keio University
• Principal Investigator: 福田 真嗣 慶應義塾大学, 政策・メディア研究科(藤沢), 特任教授 (80435677)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 腸内細菌 / 代謝物質 / メタボロゲノミクス / メタゲノム / メタボローム / ロバストネス / 環境適応 / 統合オミクス / 腸内エコシステム

Outline of Annual Research Achievements

ヒトの腸管内にはおよそ1000種類で40兆個にもおよぶとされる腸内細菌が生息しており、その集団（腸内細菌叢）は宿主腸管細胞と密接に相互作用することで、複雑な腸内生態系を形成している。近年の研究により腸内細菌叢の機能が明らかになるにつれて、その次の課題として、腸内細菌叢を含む複雑な腸内生態系全体の代謝機能をどのように制御するか、すなわち異種生物で構成される複雑な腸内生態系の代謝アダプテーションの理解とその制御という課題があげられる。そこで本研究ではマウスモデルを用いて、これまで異種生物と考えられてきた腸内細菌叢を一つの臓器として捉え、食事内容や薬剤投与などの環境因子パータベーションを与えた際の腸内環境変動について、統合オミクスアプローチや数理生物学的解析などの学際的研究手法を用いることにより、腸内細菌叢が有する代謝アダプテーション機構の理解を目指す。
本年度は昨年度から継続して実施している食事内容がもたらす腸内環境の代謝アダプテーションの理解に向けた、マウスモデルの解析を実施した。具体的には異なる脂質濃度の餌をマウスに摂食させ、その際の腸内環境についてメタボロゲノミクスアプローチにより網羅的に解析した。その結果、異なる脂質濃度により腸内環境が変動し、いくつかの腸内細菌や代謝物質が添加した脂質濃度依存的に変化することが明らかとなった。これらの情報を元に、脂質添加による腸内環境変動を予測する数理モデルの開発を進める。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] University of Michigan Medical School(米国)
• [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] Essential role of the Crk family-dosage in DiGeorge-like anomaly and metabolic homeostasis. (2020)
  • Author(s): Akira Imamoto, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, John Devany, Ocean Lu, Tomomi Kanazawa, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, Mariko Okada
  • Journal Title: Life Science Alliance Volume: - Issue: 2 Pages: e201900635-e201900635
  • DOI: 10.26508/lsa.201900635
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota (2020)
  • Author(s): Nagao-Kitamoto Hiroko, Fukuda Shinji, Higgins Peter D. R., Karlsson Niclas G., Young Vincent B., Kamada Nobuhiko, et al
  • Journal Title: Nature Medicine Volume: 26 Issue: 4 Pages: 608-617
  • DOI: 10.1038/s41591-020-0764-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of colitis with gut-microbiota dysbiosis in clathrin adapter AP-1B knockout mice (2020)
  • Author(s): Jangid Aditi, Fukuda Shinji, Seki Masahide, Horiuchi Terumi, Suzuki Yutaka, Taylor Todd D., Ohno Hiroshi, Prakash Tulika
  • Journal Title: PLoS ONE Volume: 15 Issue: 3 Pages: e0228358-e0228358
  • DOI: 10.1371/journal.pone.0228358
  • Peer Reviewed / Open Access / 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
• [Journal Article] Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease (2019)
  • Author(s): Kikuchi Koichi、Saigusa Daisuke、Kanemitsu Yoshitomi、Matsumoto Yotaro、Tsukamoto Hiroki、Abe Takaaki
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 1835-1835
  • DOI: 10.1038/s41467-019-09735-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Draft Genome Sequences of Enterococcus faecalis Strains Isolated from Healthy Japanese Individuals (2019)
  • Author(s): Tanaka Kazuki, Watabe Tsubasa, Kato Kumiko, Tsukimi Tomoya, Sato Mitsuhiko P., Odamaki Toshitaka, Tomita Masaru, Fukuda Shinji
  • Journal Title: Microbiology Resource Announcements Volume: 8 Issue: 40
  • DOI: 10.1128/mra.00832-19
  • Peer Reviewed / Open Access
• [Journal Article] Dietary l-serine confers a competitive fitness advantage to Enterobacteriaceae in the inflamed gut (2019)
  • Author(s): Kitamoto Sho, Fukuda Shinji, Barnich Nicolas, Kamada Nobuhiko, et al
  • Journal Title: Nature Microbiology Volume: 5 Issue: 1 Pages: 116-125
  • DOI: 10.1038/s41564-019-0591-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cutibacterium acnes (Propionibacterium acnes) 16S rRNA Genotyping of Microbial Samples from Possessions Contributes to Owner Identification (2019)
  • Author(s): Yang Jiayue, Tsukimi Tomoya, Yoshikawa Mia, Suzuki Kenta, Takeda Tomoki, Tomita Masaru, Fukuda Shinji
  • Journal Title: mSystems Volume: 4 Issue: 6
  • DOI: 10.1128/msystems.00594-19
  • Peer Reviewed / Open Access
• [Journal Article] A metabologenomic approach reveals changes in the intestinal environment of mice fed on American diet (2018)
  • Author(s): Ishii, C., Nakanishi, Y., Murakami, S., Nozu, R., Ueno, M., Hioki, K., Aw, W., Hirayama, A., Soga, T., Ito, M., Tomita, M., Fukuda, S.
  • Journal Title: Int. J. Mol. Sci. Volume: 19 Issue: 12 Pages: 4079-4079
  • DOI: 10.3390/ijms19124079
  • Peer Reviewed / Open Access
• [Presentation] The impact of gut microbiota-derived metabolites in health and disease (2020)
  • Author(s): Shinji Fukuda
  • Organizer: 2020 Miami Winter Symposium on Molecular mechanisms linking the microbiome and human health
  • Int'l Joint Research / Invited
• [Presentation] 腸内環境に基づく層別化医療・ヘルスケアがもたらす未来 (2020)
  • Author(s): 福田真嗣
  • Organizer: 第35回日本臨床栄養代謝学会学術集会
  • Invited
• [Presentation] 腸内環境に基づく層別化ヘルスケアがもたらす新たな予防医学 (2020)
  • Author(s): 福田真嗣
  • Organizer: 日本化学会第100春季年会
  • Invited
• [Presentation] ヒト常在細菌叢の機能理解 (2020)
  • Author(s): 福田真嗣
  • Organizer: 日本農芸化学会2020年度大会
  • Invited
• [Presentation] 第3の液性因子：腸内細菌叢由来代謝物質がもたらす機能 (2019)
  • Author(s): 福田真嗣
  • Organizer: 第92回日本内分泌学会学術集会
  • Invited
• [Presentation] 腸内環境ロバストネス因子の探索 (2019)
  • Author(s): 福田真嗣
  • Organizer: 第42回日本分子生物学会
  • Invited
• [Presentation] The impact of gut microbiota-derived metabolites in tumorigenesis (2019)
  • Author(s): Shinji Fukuda
  • Organizer: The 24th Japanese Foundation for Cancer Research-International Symposium on Cancer Chemotherapy (JFCR-ISCC)
  • Int'l Joint Research / Invited
• [Presentation] A metabologenmic approach reveals the function of gut microbiota in health and disease (2019)
  • Author(s): Shinji Fukuda
  • Organizer: The 3rd Kyoto Biomolecular Mass Spectrometry Society (KBMSS) Symposium 2019
  • Invited
• [Presentation] The impact of gut microbiota-derived metabolites in tumorigenesis (2019)
  • Author(s): Shinji Fukuda
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program, 21th International Conference on Emerging Infectious Disease in the Pacific Rim
  • Int'l Joint Research / Invited
• [Presentation] 第3の液性因子：腸内細菌叢由来代謝物質がもたらす機能 (2019)
  • Author(s): 福田真嗣
  • Organizer: 日本農芸化学会2019年度大会
  • Invited
• [Book] もっとよくわかる！腸内細菌叢 (2019)
  • Author(s): 福田真嗣
  • Total Pages: 147
  • Publisher: 羊土社
  • ISBN: 9784758122061
• [Patent(Industrial Property Rights)] 抗原結合分子、核酸組成物、ベクター組成物、細胞およびBifidobacterium longumの精製方法 (2019)
  • Inventor(s): 井上ひかる、中藤学、井上浄、福田真嗣
  • Industrial Property Rights Holder: 井上ひかる、中藤学、井上浄、福田真嗣
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019