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Human milk oligosaccharides as the bifidus factor: the mechanism underlying how bifidus flora is established in infant guts

Research Project

Project/Area Number 15H04481
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied microbiology
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) 日高 將文  東北大学, 農学研究科, 助教 (00584848)
栗原 新  石川県立大学, 生物資源環境学部, 寄附講座准教授 (20630966)
廣瀬 潤子  滋賀県立大学, 人間文化学部, 准教授 (40381917)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords母乳オリゴ糖 / ビフィズス菌 / 共生 / 共進化 / 母乳 / 酵素解析 / 酵素合成 / 酵素
Outline of Final Research Achievements

It has long been known that bifidobaceria-rich microbiota (bifidus flora) is formed in breast-fed infant intestines; however the underlying mechanism has not been elucidated. We have found that infant gut-associated bifidobacteria have an ability to assimilate human milk oligosaccharides (HMOs) that comprises the third most abundant solid component. In this study, we focused on lacto-N-biosidase, which hydrolyzes lacto-N-tetraose (the most abundant core HMO structure ), and revealed that the enzyme plays an important role in bifidus flora formation in infants. In addition, we succeeded in developing an efficient method to synthesize lacto-N-tetraose by mutating a relevant enzyme. The compound can be used for formula milk fortification.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (35 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 7 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 11 results) Remarks (3 results)

  • [Int'l Joint Research] Technical University of Denmark(Denmark)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] The University of Western Australia(Australia)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Western Australia(Australia)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] School of Chemistry and Biochemistr/The University of Western Australia(Australia)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum2017

    • Author(s)
      Yamada C, Gotoh A, Sakanaka M, Hattie M, Stubbs KA, Katayama-Ikegami A, Hirose J, Kurihara S, Arakawa T, Kitaoka M, Okuda S, Katayama T and Fushinobu S.
    • Journal Title

      Cell Chemical Biology

      Volume: 24 Issue: 4 Pages: 515-524

    • DOI

      10.1016/j.chembiol.2017.03.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Use of Gifu Anaerobic Medium for culturing 32 dominant species of human gut microbes and its evaluation based on short-chain fatty acids fermentation profiles2017

    • Author(s)
      Gotoh Aina、Nara Misaki、Sugiyama Yuta、Sakanaka Mikiyasu、Yachi Hiroyuki、Kitakata Aya、Nakagawa Akira、Minami Hiromichi、Okuda Shujiro、Katoh Toshihiko、Katayama Takane、Kurihara Shin
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 81 Issue: 10 Pages: 2009-2017

    • DOI

      10.1080/09168451.2017.1359486

    • NAID

      40022130526

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization2017

    • Author(s)
      Katoh Toshihiko、Maeshibu Takako、Kikkawa Kei-ichi、Gotoh Aina、Tomabechi Yusuke、Nakamura Motoharu、Liao Wei-Hsiang、Yamaguchi Masanori、Ashida Hisashi、Yamamoto Kenji、Katayama Takane
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 81 Issue: 10 Pages: 2018-2027

    • DOI

      10.1080/09168451.2017.1361810

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of α-l-arabinopyranosidases from human gut microbiome expands the diversity within glycoside hydrolase family 422017

    • Author(s)
      Viborg Alexander Holm、Katayama Takane、Arakawa Takatoshi、Abou Hachem Maher、Lo Leggio Leila、Kitaoka Motomitsu、Svensson Birte、Fushinobu Shinya
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 51 Pages: 21092-21101

    • DOI

      10.1074/jbc.m117.792598

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular insight into evolution of symbiosis between breast-fed infants and a member of the human gut microbiome Bifidobacterium longum2017

    • Author(s)
      Yamada C, Gotoh A, Sakanaka M, Hattie M, Stubbs KA, Katayama-Ikegami A, Hirose J, Kurihara S, Arakawa T, Kitaoka M, Okuda S, Katayama T, and Fushinobu S.
    • Journal Title

      Cell Chemical Biology

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Application study of 1,2-α-L-fucosynthase: Introduction of Fucα1-2Gal disaccharide structures on N-glycan, ganglioside, and xyloglucan oligosaccharide2016

    • Author(s)
      Sugiyama Y, Katoh T, Honda Y, Gotoh A, Ashida H, Kurihara S, Yamamoto K, and Katayama T.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 81 Issue: 2 Pages: 283-291

    • DOI

      10.1080/09168451.2016.1254532

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Introduction of H-antigens into oligosaccharides and sugar chains of glycoproteins using highly efficient 1,2-α-L-fucosynthase2016

    • Author(s)
      Sugiyama Y, Gotoh A, Katoh T, Honda Y, Yoshida E, Kurihara S, Ashida H, Kumagai H, Yamamoto K, Kitaoka M, and Katayama T.
    • Journal Title

      Glycobiology

      Volume: 26 Pages: 1235-1247

    • DOI

      10.1093/glycob/cww085

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Host-derived glycans serve as selected nutrients for the gut microbe: Human milk oligosaccharides and bifidobacteria.2016

    • Author(s)
      Takane Katayama
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 80 Issue: 4 Pages: 621-632

    • DOI

      10.1080/09168451.2015.1132153

    • NAID

      120006364097

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Gaining insight into the catalysis by GH20 lacto-N-biosidase using small molecule inhibitors and structural analysis.2015

    • Author(s)
      Hattie M, Ito T, Debowski AW, Arakawa T, Katayama T, Yamamoto K, Fushinobu S, and KA Stubbs.
    • Journal Title

      Chemical Communications (Cambridge)

      Volume: 51 Issue: 81 Pages: 15008-15011

    • DOI

      10.1039/c5cc05494j

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Novel substrate specificities of two lacto-N-biosidases towards β-linked galacto-N-biose-containing oligosaccharides of globo H, Gb5, and GA1.2015

    • Author(s)
      Gotoh A, Katoh T, Sugiyama Y, Kurihara S, Honda Y, Sakurama H, Kambe T, Ashida H, Kitaoka M, Yamamoto K, Katayama T
    • Journal Title

      Carbohydr Res

      Volume: 408 Pages: 18-24

    • DOI

      10.1016/j.carres.2015.03.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] α-N-Acetylglucosaminidase from Bifidobacterium bifidum specifically hydrolyzes α-linked N-acetylglucosamine at nonreducing terminus of O-glycan on gastric mucin2015

    • Author(s)
      芦田久ら
    • Journal Title

      Appl Microbiol Biotechnol.

      Volume: 99 Issue: 9 Pages: 3941-3948

    • DOI

      10.1007/s00253-014-6201-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 乳児のビフィズス菌とヒトミルクオリゴ糖利用2018

    • Author(s)
      片山高嶺
    • Organizer
      森永乳業創業100周年記念国際シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 母乳成分を介したビフィズス菌とヒトの共生・共進化2018

    • Author(s)
      片山高嶺
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Bifidobacterium bifidum菌株間におけるヒトミルクオリゴ糖資化様式および関連酵素の保存性2017

    • Author(s)
      後藤愛那・山田千早・苫米地祐輔・廣瀬潤子・栗原新・北岡本光・山本憲二・原田岳・何方・加藤紀彦・片山高嶺
    • Organizer
      日本農芸化学会大会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト腸内細菌が有する母乳オリゴ糖分解酵素LnbXホモログの機能解析2017

    • Author(s)
      山田千早・伏信進矢・後藤愛那・加藤紀彦・片山高嶺
    • Organizer
      日本農芸化学会大会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト母乳オリゴ糖とヒト乳脂肪から考えるビフィズス菌とヒトの共進化2017

    • Author(s)
      後藤愛那・岸野重信・岡田奈津実・廣瀬潤子・栗原新・加藤紀彦・奥田修二郎・片山高嶺・小川順
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Bifidobacterium bifidum由来1,2-α-L-フコシダーゼのN末端機能未知ドメインの解析2017

    • Author(s)
      丹沢充裕・加藤紀彦・片山高嶺
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ビフィズス菌におけるgalacto-N-biose/lacto-N-biose Iトランスポーターの多様性解析2017

    • Author(s)
      阪中幹祥・石田卓也・佐藤真与・谷内寛之・阿部紘一・前田信悟・吹谷智・横田篤・栗原新・荒川孝俊・五十嵐圭日子・伏信進矢・片山高嶺
    • Organizer
      2017年度乳酸菌学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Symbiosis and co-evolution between breast-fed infants and Biofidobacterium driven by human milk oligosaccharides and their degrading enzymes2017

    • Author(s)
      Takane Katayama
    • Organizer
      The 26th Gut microflora symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Physiological characterization of 2’-fucosyllactose transport systems from Bifidobacterium longum subsp. infantis2016

    • Author(s)
      Sakanaka, M., Yachi, H., Kurihara, S., Fukiya, S., Yokota, A., Katayama, T.
    • Organizer
      Probio-Bifido 2016
    • Place of Presentation
      Cork, Ireland
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 微生物酵素から考える腸内細菌とヒトの共生〜ビフィズス菌と母乳オリゴ糖〜2016

    • Author(s)
      片山高嶺
    • Organizer
      日本農芸化学会2015年度大会シンポジウム
    • Place of Presentation
      北海道
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腸内細菌を制御するオリゴ糖ービフィズス菌と母乳オリゴ糖ー2016

    • Author(s)
      片山高嶺
    • Organizer
      第21回フードファクター学会学術集会
    • Place of Presentation
      富山
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 母乳オリゴ糖とビフィズス菌-共生と共進化-.2016

    • Author(s)
      片山高嶺
    • Organizer
      第109回発酵学懇話会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ビフィズス因子としての母乳オリゴ糖2016

    • Author(s)
      片山高嶺
    • Organizer
      第33回日本微量栄養素学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ビフィズス菌と母乳オリゴ糖〜ビフィズスフローラ形成の分子機序解明を目指して〜2015

    • Author(s)
      片山高嶺
    • Organizer
      日本農芸化学会・産学官若手交流会さんわか第25回セミナー
    • Place of Presentation
      京都
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] カギの穴から天を覗く~ビフィズス菌酵素から考えるヒトとの共生~2015

    • Author(s)
      片山高嶺
    • Organizer
      平成27年度日本乳酸菌学会秋期セミナー
    • Place of Presentation
      東京
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Unique Carbohydrate Metabolism in Bifidobacteria2015

    • Author(s)
      Takane Katayama
    • Organizer
      JSPS France Japan Joint Forum, Science of Fermentation
    • Place of Presentation
      フランス・ディジョン
    • Year and Date
      2015-11-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒトミルクオリゴ糖と乳児型ビフィズス菌〜共生と共進化〜2015

    • Author(s)
      片山高嶺
    • Organizer
      平成27年度酪農科学シンポジウム
    • Place of Presentation
      帯広
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Remarks] 分子応答機構学分野HP

    • URL

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

    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2016 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

      http://www.bunshioutou.lif.kyoto-u.ac.jp/katayama/Publications.html

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-12-27  

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