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Enzymatic insight into the microbiota formation in infant guts

Research Project

Project/Area Number 21H02116
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38030:Applied biochemistry-related
Research InstitutionKyoto University

Principal Investigator

Katayama Takane  京都大学, 生命科学研究科, 教授 (70346104)

Co-Investigator(Kenkyū-buntansha) 伏信 進矢  東京大学, 大学院農学生命科学研究科(農学部), 教授 (00302589)
奥田 修二郎  新潟大学, 医歯学系, 教授 (00512310)
北岡 本光  新潟大学, 自然科学系, 教授 (60353984)
杉山 友太  群馬大学, 食健康科学教育研究センター, 助教 (80908749)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2023: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywords共生 / ムチンO-グリカン / ヒト母乳オリゴ糖 / ビフィズス菌 / 酵素機能解析 / 母乳オリゴ糖 / ムチン糖鎖 / 糖鎖 / スルホグルコシダーゼ / 腸内細菌 / 代謝物 / 転写因子 / 共生・共進化
Outline of Research at the Start

次世代シークエンサーが普及しはじめた2010年代以降、メタゲノム解析の報告例が増加し、遺伝子のアノテーションから腸内細菌代謝が議論されることが多くなった。しかしながら、ホモロジー検索を起点とした通常のインフォマティクス解析では、腸内において細菌増殖の基質(エサ)となる糖質の構造(糖鎖の結合様式や鎖長)に対する作用を考慮して議論することは出来ず、細菌の代謝を正確に把握しているとは言い難い。申請者は、細菌酵素の特異性や代謝機能を酵素化学的および構造生物学的に精密に理解した上で、それらをインフォマティクス解析に反映させることが重要であると考えており、主に乳児期における菌叢形成を対象に研究を進める。

Outline of Final Research Achievements

Gut microbiota formed during infancy significantly influences immune development. We have elucidated that the oligosaccharides abundantly present in human milk (human milk oligosaccharides) are responsible for the formation of bifidobacteria-rich microbiota in the gut of breastfed infants. This study aimed to understand how naturally diversified amino acid replacements in bacterial enzymes affect the formation of gut microbiota. As a result, we succeeded in establishing a framework that enables us to understand the molecular basis underlying gut microbiota formation and to more precisely analyze gut microbial metagenomic data.

Academic Significance and Societal Importance of the Research Achievements

腸内細菌およびその代謝物が宿主の健康に大きく関与することが知られている一方で、腸内細菌叢の形成機構については未解明な点が多く残されている。本研究では、腸内細菌が有する酵素のユニークな機能的差異に着目し、その差異が菌叢形成にどのような影響を及ぼすのかについて、微生物代謝および酵素機能の観点から明らかとした。腸内細菌の菌叢解析(菌種組成解析)やメタゲノム解析(環境DNA全解析)が行われているが、腸内細菌が有する酵素(代謝能)は、菌種レベルのみならず菌株レベルで異なっていることから、菌叢形成機序を理解するためには、より詳細な酵素機能の解析やインフォマティクス解析が必要であることが判明した。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (26 results)

All 2023 2022 2021 Other

All Int'l Joint Research (8 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 7 results) Remarks (3 results)

  • [Int'l Joint Research] The University of Western Australia(オーストラリア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Wageningen University(オランダ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Sanford Burnham Prebys/Georgia Institute of Technology(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] The University of Western Australia(オーストラリア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University College Cork(アイルランド)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Wageningen University(オランダ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] The Technical University of Denmark(デンマーク)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Sanford Burnham Prebys Institute(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] A bacterial sulfoglycosidase highlights mucin O-glycan breakdown in the gut ecosystem2023

    • Author(s)
      Katoh T, Yamada C, Wallace M, Yoshida A, Gotoh A, Arai M, Maeshibu T, Kashima T, Hagenbeek A, Ojima MN, Takada H, Sakanaka M, Shimizu H, Nishiyama K, Ashida H, Hirose J, Suarez-Diez M, Nishiyama M, Kimura I, Stubbs KA, Fushinobu S, Katayama T
    • Journal Title

      Nature Chemical Biology

      Volume: - Issue: 6 Pages: 778-789

    • DOI

      10.1038/s41589-023-01272-y

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Substrate recognition mode of a glycoside hydrolase family 42 β-galactosidase from Bifidobacterium longum subspecies infantis(BiBga42A) revealed by crystallographic and mutational analyses2023

    • Author(s)
      Gotoh Aina、Hidaka Masafumi、Sakurama Haruko、Nishimoto Mamoru、Kitaoka Motomitsu、Sakanaka Mikiyasu、Fushinobu Shinya、Katayama Takane
    • Journal Title

      Microbiome Research Reports

      Volume: 2 Pages: 20-20

    • DOI

      10.20517/mrr.2023.14

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GH20 and GH84 β-N-acetylglucosaminidases with different linkage specificities underpin mucin O-glycan breakdown capability of Bifidobacterium bifidum2023

    • Author(s)
      Takada Hiromi、Katoh Toshihiko、Sakanaka Mikiyasu、Odamaki Toshitaka、Katayama Takane
    • Journal Title

      Journal of Biological Chemistry

      Volume: 299 Issue: 6 Pages: 104781-104781

    • DOI

      10.1016/j.jbc.2023.104781

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structures of glycoside hydrolase family 136 lacto-N-biosidases from monkey gut- and human adult gut bacteria2022

    • Author(s)
      Chihaya Yamada, Takane Katayama , Shinya Fushinobu
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 86 Issue: 4 Pages: 464-475

    • DOI

      10.1093/bbb/zbac015

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human Milk Oligosaccharide Utilization in Intestinal Bifidobacteria Is Governed by Global Transcriptional Regulator NagR2022

    • Author(s)
      Arzamasov Aleksandr A.、Nakajima Aruto、Sakanaka Mikiyasu、Ojima Miriam N.、Katayama Takane、Rodionov Dmitry A.、Osterman Andrei L.
    • Journal Title

      mSystems

      Volume: 7 Issue: 5

    • DOI

      10.1128/msystems.00343-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Priority effects shape the structure of infant-type Bifidobacterium communities on human milk oligosaccharides2022

    • Author(s)
      Ojima Miriam N.、Jiang Lin、Arzamasov Aleksandr A.、Yoshida Keisuke、Odamaki Toshitaka、Xiao Jinzhong、Nakajima Aruto、Kitaoka Motomitsu、Hirose Junko、Urashima Tadasu、Katoh Toshihiko、Gotoh Aina、van Sinderen Douwe、Rodionov Dmitry A.、Osterman Andrei L.、Sakanaka Mikiyasu、Katayama Takane
    • Journal Title

      The ISME Journal

      Volume: 16 Issue: 9 Pages: 2265-2279

    • DOI

      10.1038/s41396-022-01270-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diversification of a Fucosyllactose Transporter within the Genus Bifidobacterium2022

    • Author(s)
      Ojima Miriam N.、Asao Yuya、Nakajima Aruto、Katoh Toshihiko、Kitaoka Motomitsu、Gotoh Aina、Hirose Junko、Urashima Tadasu、Fukiya Satoru、Yokota Atsushi、Abou Hachem Maher、Sakanaka Mikiyasu、Katayama Takane
    • Journal Title

      Applied and Environmental Microbiology

      Volume: 88 Issue: 2

    • DOI

      10.1128/aem.01437-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] A carbohydrate-binding module (CBM)-dependent mucin O-glycan breakdown strategy of Bifidobacterium bifidum, highlighted by sulfoglycosidase BbhII2023

    • Author(s)
      Takane Katayama
    • Organizer
      The 13th Asian Conference on Lactic Acid Bacteria
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Host glycan-mediated symbiosis between bifidobacteria and humans2023

    • Author(s)
      Takane Katayama
    • Organizer
      Korean Society for Lactic Acid Bacteria and Probiotics
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ミルクオリゴ糖とムチン糖鎖を介した ヒトとビフィズス菌の共生2023

    • Author(s)
      片山高嶺
    • Organizer
      食品免疫学会第16回産学官交流委員会主催セミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] オリゴ糖が有するプレバイオティクス効果の 分子基盤と応用展開2022

    • Author(s)
      片山高嶺
    • Organizer
      第74回日本生物工学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 酵素のカギ穴から考える ヒトとビフィズス菌の共生2022

    • Author(s)
      片山高嶺
    • Organizer
      第19回糖鎖科学コンソーシアムシンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 腸内細菌によるムチン型糖鎖の分解は 宿主の健康・疾患に関わる2022

    • Author(s)
      片山高嶺
    • Organizer
      日本農芸化学会2022年度大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Enzymes involved in mucin O-glycan degradation by Bifidobacterium bifidum2022

    • Author(s)
      Takane Katayama
    • Organizer
      International Symposium on Microbial Glycoconjugates and the GlySpace Alliance
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Adaptive strategy of bifidobacteria to assimilate human milk oligosaccharides in breastfed infant gut2021

    • Author(s)
      Takane Katayama
    • Organizer
      The 11th Asian Conference on Lactic Acid Bacteria
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] https://www.bunshioutou.lif.kyoto-u.ac.jp/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 京都大学大学院生命科学研究科分子応答機構学分野

    • URL

      https://www.bunshioutou.lif.kyoto-u.ac.jp/Home.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 京都大学大学院生命科学研究科分子応答機構学

    • URL

      https://www.bunshioutou.lif.kyoto-u.ac.jp/katayama/Home.html

    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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