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Production of functional substances derived from fatty acids in human milk fat by Bifidobacterium

Research Project

Project/Area Number 19K15732
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 38020:Applied microbiology-related
Research InstitutionKyoto University

Principal Investigator

Gotoh Aina  京都大学, 生命科学研究科, 特別研究員(PD) (60738384)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords母乳 / ビフィズス菌 / HYA / LA / 脂質 / 腸管バリア機能 / 脂肪酸 / 乳児 / リノール酸 / 共生
Outline of Research at the Start

本研究では、「ビフィズスフローラ形成のヒトにおける生理的意義」を、脂質代謝を基軸として理解することを目的とする。
近年、人乳にも含まれるリノール酸の水和物であるHYAに腸管バリア機能を高める作用があることなどが明らかとなった。申請者は母乳および乳児糞便を解析し、乳児糞便にのみHYAが検出されること、ビフィズス菌がin vitroでHYA産生能を持つことを確認した。今後、多数の母子ペアサンプルの分析とビフィズスフローラの相関解析、ビフィズス菌によるHYA 産生誘導条件を探索する。
その成果は、ヒトとビフィズス菌の共生・共進化を解明するのみならず、より人乳に近い調整乳の開発に繋がるであろう。

Outline of Final Research Achievements

Breast-fed infants generally have gut microbiota dominated by bifidobacteria. However, reason of why humans have selected bifidobacteria remains unanswered.We analyzed oils of mother's milk and infant's feces, and showed that HYA, which stimulates epithelial barrier function, is detected in only infant’s feces. We inferred that HYA was produced from conversion of LA, an essential fatty acid contained in breast milk, by gut microbes. Microbiota analysis revealed the strong correlation between the cell counts of genus Bifidobacterium and the conversion ratio of LA to HYA in infant stools. In addition, we demonstrated that Bifidobacterium and purified enzymes of Bifidobacterium convert LA to HYA in vitro assay. Interestingly, it was found thatt the comversion ability was different among the species. In human, infant-gut assocated bifidobacterium grown by oligosaccharides may enhance HYA production, thereby fortifying the barrier function of intestinal cells of vulnerable infants.

Academic Significance and Societal Importance of the Research Achievements

宿主と腸内細菌の関係は、主にオミクス的アプローチから研究され、重要な知見がもたらされた。それらを基盤とし、疾病治療、健康機能食品への応用が広く期待されている。それに伴い、両者の関連を物質や遺伝子レベルのメカニズムとして説明することが求められるようになってきたが、従来のオミクス研究だけではその達成は難しい。
本研究は、ビフィズス菌という特定の菌種、母乳中のLAとHYAという特定の物質に絞った解析を行うものである。これは、宿主由来物質・菌・遺伝子・機能物質というそれぞれ具体的な因子を、一連のメカニズムとして明らかにしたものであり、今後の腸内細菌研究が目指すべき新しい形を示すものである。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 2020 2019

All Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [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
  • [Journal Article] Next-generation prebiotic promotes selective growth of bifidobacteria, suppressing Clostridioides difficile2021

    • Author(s)
      Hirano R., Sakanaka M., Yoshimi K., Sugimoto N., Eguchi S., Yamauchi Y., Nara M., Maeda S., Ami Y., Gotoh A., Katayama T., Iida N., Kato T., Ohno H., Fukiya S., Yokota A., Nishimoto M., Kitaoka M., Nakai H., Kurihara S.
    • Journal Title

      Gut microbes

      Volume: 13 Issue: 1 Pages: 1973835-1973835

    • DOI

      10.1080/19490976.2021.1973835

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bifidobacterium bifidum Suppresses Gut Inflammation Caused by Repeated Antibiotic Disturbance Without Recovering Gut Microbiome Diversity in Mice2020

    • Author(s)
      M. N. Ojima, A. Gotoh, H. Takada, T. Odamaki, J. Xiao, T. Katoh, T. Katayama
    • Journal Title

      Front Microbiol .

      Volume: 18;11 Pages: 1349-1349

    • DOI

      10.3389/fmicb.2020.01349

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways2020

    • Author(s)
      M. J. Pichler, C. Yamada, B. Shuoker, C. Alvarez-Silva, A. Gotoh, M. L. Leth, E. Schoof, T. Katoh, M. Sakanaka, T. Katayama, C. Jin, N. G. Karlsson, M. Arumugam, S. Fushinobu, Maher A. Hachem
    • Journal Title

      Nat Commun.

      Volume: 3;11(1) Issue: 1 Pages: 3285-3285

    • DOI

      10.1038/s41467-020-17075-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bifidobacterium bifidum to Host Glycans, Viewed from Glycoside Hydrolyases and Carbohydrate-Binding Modules.2020

    • Author(s)
      Katoh T, Ojima MN, Sakanaka M, Ashida H, Gotoh A, and Katayama T
    • Journal Title

      Microorganisms.

      Volume: 8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evolutionary adaptation in fucosyllactose uptake systems supports bifidobacteria-infant symbiosis.2019

    • Author(s)
      Sakanaka M, Hansen ME, Gotoh A, Katoh T, Yoshida K, Odamaki T, Yachi H, Sugiyama Y, Kurihara S, Hirose J, Urashima T, Xiao JZ, Kitaoka M, Fukiya S, Yokota A, Lo Leggio L, Abou Hachem M, and Katayama T
    • Journal Title

      Sci Adv

      Volume: 28;5

    • NAID

      120006716596

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Varied Pathways of Infant Gut-Associated Bifidobacterium to Assimilate Human Milk Oligosaccharides: Prevalence of the Gene Set and Its Correlation with Bifidobacteria-Rich Microbiota Formation.2019

    • Author(s)
      Sakanaka M, Gotoh A, Yoshida K, Odamaki T, Koguchi H, Xiao JZ, Kitaoka M, and Katayama T
    • Journal Title

      Nutrients

      Volume: 26;12

    • NAID

      120006784431

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 嫌気性腸内細菌と腸上皮細胞の共培養を可能とするフロー型アピカル嫌気培養器の開発2021

    • Author(s)
      後藤 愛那、橋本 豊之、米田 恭子、藤山 陽一、小関 英一、加藤 紀彦、田川 陽一、金 倫基、長谷 耕二、片山 高嶺
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Enzymatic synthesis of lacto-N-tetraose, a core structure of human milk oligosaccharide, using mutant phosphorylase.2019

    • Author(s)
      Katoh T, Gotoh A, Norioka T, Kitaoka M, and Katayama T
    • Organizer
      The 1st Japan-Switzerland-Germany workshop for enzyme technology and bioprocess development.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Probiotic Bifidobacterium bifidum Alters the Gut Microbiome after Repeated Antibiotic Disturbance but Contributes to the Recovery of Host Health.2019

    • Author(s)
      Ojima MN, Gotoh A, Takada H, Katoh T, and Katayama T
    • Organizer
      ASM Microbe.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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