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

• Project/Area Number: 15H04481
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied microbiology
• Research Institution: Kyoto 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: ¥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.

Research Products

• [Int'l Joint Research] Technical University of Denmark(Denmark)
• [Int'l Joint Research] The University of Western Australia(Australia)
• [Int'l Joint Research] University of Western Australia(Australia)
• [Int'l Joint Research] School of Chemistry and Biochemistr/The University of Western Australia(Australia)
• [Journal Article] Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum (2017)
  • 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
  • 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 profiles (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Discovery of α-l-arabinopyranosidases from human gut microbiome expands the diversity within glycoside hydrolase family 42 (2017)
  • 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
  • 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 longum (2017)
  • 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
  • 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 oligosaccharide (2016)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Introduction of H-antigens into oligosaccharides and sugar chains of glycoproteins using highly efficient 1,2-α-L-fucosynthase (2016)
  • 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
  • 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
  • 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
  • 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
  • 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 mucin (2015)
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [Presentation] Symbiosis and co-evolution between breast-fed infants and Biofidobacterium driven by human milk oligosaccharides and their degrading enzymes (2017)
  • Author(s): Takane Katayama
  • Organizer: The 26th Gut microflora symposium
  • Int'l Joint Research / Invited
• [Presentation] Physiological characterization of 2’-fucosyllactose transport systems from Bifidobacterium longum subsp. infantis (2016)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Invited
• [Presentation] Unique Carbohydrate Metabolism in Bifidobacteria (2015)
  • 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
  • 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
  • Invited
• [Remarks] 分子応答機構学分野HP
  • URL: http://www.bunshioutou.lif.kyoto-u.ac.jp/katayama/Home.html
• [Remarks]
  • URL: http://www.bunshioutou.lif.kyoto-u.ac.jp/katayama/Home.html
• [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