Metabolomic approach to oral biofilm and saliva: possible risk indicator for oral diseases

2013 Fiscal Year Final Research Report

• Project/Area Number: 22390399
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Social dentistry
• Research Institution: Tohoku University
• Principal Investigator: TAKAHASHI Nobuhiro 東北大学, 歯学研究科(研究院), 教授 (60183852)
• Co-Investigator(Kenkyū-buntansha): KOSEKI Takeyoshi 東北大学, 大学院・歯学研究科, 教授 (80291128) ; SENPUKU Hidenobu 国立感染症研究所, 細菌第一部, 部長 (20250186) ; SAKAMOATO Mitsuo 独立行政法人理化学研究所, 微生物材料開発室, 協力研究員 (50321766) ; WASHIO Jumpei 東北大学, 大学院・歯学研究科, 助教 (20400260)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Keywords: 口腔バイオフィルム / 唾液 / メタボローム / 微生物 / 糖代謝 / アミノ酸代謝 / 糖アルコール

Research Abstract

Metabolome analysis for oral biofilm and saliva using CE-TOFMS was established. This method made it possible to analyze not only sugar metabolism but also amino acid metabolism in oral biofilm and even in saliva, where only small amount of metabolites (about 1/100 of oral biofilm) was contained. In addition, the analyses of the effect of sugar alcohols and fluorides on the biofilm metabolism suggested close coordination between sugar and amino acid metabolisms. Metabolome profiles of sugar and amino acid metabolisms can be used for risk indicators of dental caries and periodontitis/oral malodor, respectively.

Research Products

• [Journal Article] Responses of infected dental pulp to αTCP containing antimicrobials in rat molars (2014)
  • Author(s): Sato T, Kenmotsu S, Nakakura-Ohshima K, Takahashi N, Ohshima H
  • Journal Title: Arch Histol Cytol Volume: 75 (in press)
  • URL: http://www.ishc.net/
  • Peer Reviewed
• [Journal Article] Microbiologically induced corrosive properties of the titanium surface (2014)
  • Author(s): Fukushima A, Mayanagi G, Nakajo K, Sasaki K, Takahashi N
  • Journal Title: J Dent Res Volume: 93(5) Pages: 525-529
  • DOI: 10.1177/0022034514524782
  • Peer Reviewed
• [Journal Article] Effect of fluoride-releasing restorative materials on bacteria-induced pH fall at the bacteria -material interface : An in vitro model study (2014)
  • Author(s): Mayanagi G, Igarashi K, Washio J, Domon-Tawaraya H, Takahashi N
  • Journal Title: J Dent Volume: 42(1) Pages: 15-20
  • DOI: 10.1016/j.jdent.2013.11.006
  • Peer Reviewed
• [Journal Article] Fluoride-sensitivity of growth and acid production of oral Actinomyces : comparison with oral Streptococcus (2013)
  • Author(s): Kawashima J, Nakajo K, Washio J, Mayanagi G, Shimauchi H, Takahashi N
  • Journal Title: Microbiol Immunol Volume: 57(12) Pages: 797-804
  • DOI: 10.1111/1348-0421.12098
  • Peer Reviewed
• [Journal Article] A high-sensitive and non-radioisotopic fluorescence dye method for evaluating bacterial adhesion to denture materials (2013)
  • Author(s): Sakuma Y, Washio J, Sasaki K, Takahashi N
  • Journal Title: Dent Mater J Volume: 32(4) Pages: 585-591
  • URL: https://www.jstage.jst.go.jp/browse/dmj
  • Peer Reviewed
• [Journal Article] Divalent cations enhance fluoride binding to Streptococcus mutans and Streptococcus sanguinis cells and subsequently inhibit bacterial acid production (2013)
  • Author(s): Domon-Tawaraya H, Nakajo K, Washio J, Ashizawa T, Ichino T, Sugawara H, Fukumoto S, Takahashi N
  • Journal Title: Caries Res Volume: 47(2) Pages: 141-149
  • DOI: 10.1159/000344014
  • Peer Reviewed
• [Journal Article] Dental caries from a molecular microbiological perspective (2013)
  • Author(s): Nyvad B, Crielaard W, Mira A, Takahashi N, Beighton D
  • Journal Title: Caries Res Volume: 47(2) Pages: 89-102
  • DOI: 10.1159/000345367
  • Peer Reviewed
• [Journal Article] Effects of a coating resin containing S-PRG filler to prevent demineralization of root surfaces (2012)
  • Author(s): Ma S, Imazato S, Chen J-H, Mayanagi G, Takahashi N, Ishimoto T, Nakano T
  • Journal Title: Dent Mater J Volume: 31(6) Pages: 909-915
  • URL: https://www.jstage.jst.go.jp/browse/dmj
  • Peer Reviewed
• [Journal Article] Metabolomic approach to oral biofilm characterization - A future direction of biofilm research (2012)
  • Author(s): Takahashi N, Washio J, Mayanagi G
  • Journal Title: J Oral Biosci Volume: 54(3) Pages: 138-143
  • URL: http://www.journals.elsevier.com/journal-of-oral-biosciences/
  • Peer Reviewed
• [Journal Article] Quantification and identification of bacteria in acrylic resin denture bases and dento-maxillary obturator-prostheses (2012)
  • Author(s): Takeuchi Y, Nakajo K, Sato T, Koyama S, Sasaki K, Takahashi N
  • Journal Title: Am J Dent Volume: 25(3) Pages: 171-175
  • URL: http://www.amjdent.com/
  • Peer Reviewed
• [Journal Article] Microbial composition of dental plaque microflora on first molars with orthodontic bands and brackets, and the acidogenic potential of these bacteria (2012)
  • Author(s): Komori R, Sato T, Takano-Yamamoto T, Takahashi N
  • Journal Title: J Oral Biosci Volume: 54(2) Pages: 107-112
  • URL: http://www.journals.elsevier.com/journal-of-oral-biosciences/
  • Peer Reviewed
• [Journal Article] Rapid quantification of bacteria in infected root canals using fluorescence filter : A pilot study on its clinical application to the evaluation of the outcomes of endodontic treatment (2012)
  • Author(s): Sato T, Yamaki K, Ishida N, Shoji M, Sato E, Abiko Y, Hashimoto K, Takeuchi Y, Matsuyama J, Shimauchi H, Takahashi N
  • Journal Title: Int J Dent Volume: Volume 2012(Article ID 172935) Pages: 4
  • DOI: 10.1155/2012/172935
  • Peer Reviewed
• [Journal Article] Cultivable anaerobic microbiota of infected root canals (2012)
  • Author(s): Sato T, Yamaki K, Ishida N, Hashimoto K, Takeuchi Y, Shoji M, Sato E, Matsuyama J, Shimauchi H, Takahashi N
  • Journal Title: Int J Dent Volume: Volume 2012(Article ID 609689) Pages: 5
  • DOI: 10.1155/2012/609689
  • Peer Reviewed
• [Journal Article] Microflora profiling of infected root canal before and after treatment using culture-independent methods (2012)
  • Author(s): Ito Y, Sato T, Yamaki K, Mayanagi G, Hashimoto K, Shimauchi H, Takahashi N
  • Journal Title: J Microbiol Volume: 50(1) Pages: 58-62
  • DOI: 10.1007/s12275-012-0459-4
  • Peer Reviewed
• [Journal Article] Profiling of dental plaque microflora on root caries lesions and the protein-denaturing activity of these bacteria (2011)
  • Author(s): Hashimoto K, Sato T, Shimauchi H, Takahashi N
  • Journal Title: Am J Dent Volume: 24(5) Pages: 295-299
  • URL: http://www.amjdent.com/
  • Peer Reviewed
• [Journal Article] Evaluation of pH at the bacteria-dental cement interface (2011)
  • Author(s): Mayanagi G, Igarashi K, Washio J, Nakajo K, Domon-Tawaraya H, Takahashi N
  • Journal Title: J Dent Res Volume: 90(12) Pages: 1446-1450
  • DOI: 10.1177/0022034511423392
  • Peer Reviewed
• [Journal Article] Metabolomic effects of xylitol and fluoride on plaque biofilm in vivo (2011)
  • Author(s): Takahashi N, Washio J
  • Journal Title: J Dent Res Volume: 90(12) Pages: 1463-1468
  • DOI: 10.1177/0022034511423395
  • Peer Reviewed
• [Journal Article] Effects of the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) on bacterial viability and metabolism (2011)
  • Author(s): Izutani N, Imazato S, Nakajo K, Takahashi N, Takahashi Y, Ebisu S, Russell RRB
  • Journal Title: Eur J Oral Sci Volume: 119(2) Pages: 175-181
  • DOI: 10.1111/j.1600-0722.2011.00817.x
  • Peer Reviewed
• [Journal Article] The role of bacteria in the caries process : ecological perspectives (2011)
  • Author(s): Takahashi N, Nyvad B
  • Journal Title: J Dent Res Volume: 90(3) Pages: 294-303
  • DOI: 10.1177/0022034510379602
  • Peer Reviewed
• [Journal Article] Detection and identification of non-Candida albicans species in human oral lichen planus (2011)
  • Author(s): Masaki M, Sato T, Sugawara Y, Sasano T, Takahashi N
  • Journal Title: Microbiol Immunol Volume: 55(1) Pages: 66-70
  • DOI: 10.1111/j.1348-0421.2010.00285.x
  • Peer Reviewed
• [Journal Article] Metabolomics of supragingival plaque and oral bacteria (2010)
  • Author(s): Takahashi N, Washio J, Mayanagi G
  • Journal Title: J Dent Res Volume: 89(12) Pages: 1383-1388
  • DOI: 10.1177/0022034510377792
  • Peer Reviewed
• [Journal Article] Autoactivation of proteolytic activity in human whole saliva (2010)
  • Author(s): Miyoshi Y, Watanabe M, Takahashi N
  • Journal Title: J Oral Biosci Volume: 52(4) Pages: 402-408
  • URL: http://www.journals.elsevier.com/journal-of-oral-biosciences/
  • Peer Reviewed
• [Journal Article] Ammonia concentration and pH-lowering activity of marginal dental plaque from teeth with and without periodontitis (2010)
  • Author(s): Kumagami T, Shimizu K, Igarashi K, Takahashi N
  • Journal Title: J Dent Hlth Volume: 60(5) Pages: 563-568
  • URL: http://www.kokuhoken.or.jp/jsdh/journal.html
  • Peer Reviewed
• [Journal Article] Resistance to acidic environments of caries-associated bacteria : Bifidobacterium dentium and Bifidobacterium longum (2010)
  • Author(s): Nakajo K, Takahashi N, Beighton D
  • Journal Title: Caries Res Volume: 44(5) Pages: 431-437
  • DOI: 10.1159/000318582
  • Peer Reviewed
• [Journal Article] (Review : New strategy of study for oral microbiology) Challenge to metabolomics of oral biofilm-from "what are they?" to "what are they doing?" (2010)
  • Author(s): Washio J, Mayanagi G, Takahashi N
  • Journal Title: J Oral Biosci Volume: 52(3) Pages: 225-232
  • URL: http://www.journals.elsevier.com/journal-of-oral-biosciences/
  • Peer Reviewed
• [Journal Article] Profiling of subgingival plaque biofilm microflora from periodontally healthy subjects and from subjects with periodontitis using quantitative real-time PCR (2010)
  • Author(s): Abiko Y, Sato T, Mayanagi G, Takahashi N
  • Journal Title: J Periodont Res Volume: 45(3) Pages: 389-395
  • DOI: 10.1111/j.1600-0765.2009.01250.x
  • Peer Reviewed
• [Presentation] ヒト・プラークの糖アルコール代謝 : メタボロミクス的アプローチ (2013)
  • Author(s): 鷲尾純平, 高橋信博
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山, (J Oral Biosci Supplement: p. 221, 2013. (Abstract #P2-150))
  • Year and Date: 2013-09-22
• [Presentation] メタボローム解析による口腔扁平上皮癌のエネルギー代謝特性の解明とバイオマーカーの探索 (2013)
  • Author(s): 小川珠生, 鷲尾純平, 高橋哲, 高橋信博
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山, (J Oral Biosci Supplement: p. 158, 2013. (Abstract #P1-86))
  • Year and Date: 2013-09-21
• [Presentation] Pathognomonic Glutamine Metabolism in Oral Squamous Cell Carcinoma -Metabolomic Approach- (2013)
  • Author(s): Ogawa T, Washio J, Takahashi T, Takahashi N
  • Organizer: The 2nd IADR-APR (Asia Pacific Region)
  • URL: http://www.dentalresearch.org
  • Place of Presentation: Bangkok, Thailand (J Dent Res 92 Spec Iss B: 336, 2013)
  • Year and Date: 2013-08-21
• [Presentation] Overview : Parasite: Oral biofilm in health and disease-holistic approach by "Omics" (2013)
  • Author(s): Takahashi N
  • Organizer: Peking-Tohoku Dental Symposium : Innovative Research for Biosis-Abiosis Intelligent Interface
  • Place of Presentation: Beijing, China
  • Year and Date: 2013-07-26
• [Presentation] 口腔生態系から見た口臭～生化学的,生態学的アプローチ～ (2013)
  • Author(s): 高橋信博
  • Organizer: 第4回日本口臭学会学術大会
  • Place of Presentation: 鶴見(教育講演1)
  • Year and Date: 2013-07-13
• [Presentation] プラークと唾液のメタボローム解析-口腔内でのアミノ酸の利用に注目して- (2012)
  • Author(s): 鈴木啓佑, 月星陽介, 渡邊基博, 小川珠生, 鷲尾純平, 高橋信博
  • Organizer: 第22回日本歯科医学会総会
  • Place of Presentation: 大阪, (日本歯科医師会雑誌 65(5): 686, 2012(Abstract #DSP013))
  • Year and Date: 2012-11-11
• [Presentation] メタボローム解析で見えてきた口腔バイオフィルムの機能-「何がいるか」から「何をしているか」- (2012)
  • Author(s): 鷲尾純平, 真柳弦, 小川珠生, 高橋信博
  • Organizer: 第22回日本歯科医学会総会
  • Place of Presentation: 大阪, (日本歯科医師会雑誌 65(5): 616, 2012(Abstract #P025))
  • Year and Date: 2012-11-10
• [Presentation] Dental plaque biofilm中のアミノ酸の代謝機構-CE-TOFMS を用いたメタボロミクス的観点から-, The composition and the utilization of amino acids in dental plaque biofilm -Metabolomics approach with CE-TOFMS- (2012)
  • Author(s): 鷲尾純平, 高橋信博
  • Organizer: 第54回歯科基礎医学会学術大会
  • Place of Presentation: 郡山, (J Oral Biosci Supplement: p. 141, 2012. (Abstract #P2-15))
  • Year and Date: 2012-09-16
• [Presentation] Amino acid composition and amino-acid degrading activity of dental plaque (2012)
  • Author(s): Washio J, Ogawa T, Suzuki K, Tsukiboshi Y, Watanabe M, Takahashi N
  • Place of Presentation: Iguacu Falls, Brazil, (J Dent Res 91(Special Issue B): 586, 2012)
  • Year and Date: 2012-06-21
• [Presentation] CE-TOFMS を用いた口腔プラークバイオフィルムの糖代謝メタボローム解析～フッ化物やキシリトールによる影響をin vivo で探る～ (2011)
  • Author(s): 鷲尾純平, 小川珠生, 真柳弦, 高橋信博
  • Organizer: キャピラリー電気泳動シンポジウム
  • Place of Presentation: 鶴岡
  • Year and Date: 20111109-11
• [Presentation] Recent discoveries about the metabolism of microbial communities and caries-associated microorganisms (2011)
  • Author(s): Takahashi N
  • Organizer: ORCA symposium
  • Place of Presentation: Kaunas, Lithuania
  • Year and Date: 20110706-09
• [Presentation] ヒト・プラークの糖代謝に対するフッ化物およびキシリトールの影響～CE-TOFMS を用いたメタボロミクス・アプローチ～ (2011)
  • Author(s): 鷲尾純平, 高橋信博
  • Organizer: 第53回歯科基礎医学会学術大会
  • Place of Presentation: 岐阜, (J Oral Biosci 53(S): 139, 2011)
  • Year and Date: 2011-10-01
• [Presentation] Metabolomic approach to oral biofilm characterization. Satellite Symposium "Leading edge of oral biofilm research - Challenge for correct understanding of oral disease caused by biofilm-" (2011)
  • Author(s): Takahashi N
  • Organizer: The 53rd Annual Meeting of Japanese Association for Oral Biology
  • Place of Presentation: Gifu, Japan, (Oral Biosci 53(S): 91, 2011)
  • Year and Date: 2011-09-30
• [Presentation] ヒトプラークとう蝕関連口腔細菌Streptococcus mutansの糖代謝に対するキシリトールの影響の相違 (2011)
  • Author(s): 鷲尾純平, 高橋信博
  • Organizer: 第84回日本生化学大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] Metabolome analysis of oral plaque biofilm using CE-TOFMS (2011)
  • Author(s): Washio J, Mayanagi G, Takahashi N
  • Organizer: The 4th International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai, (Program and Abstracts of the International Symposium for Interface Oral Health Science, p.75)
  • Year and Date: 2011-03-08
• [Presentation] Metabolomic approach to oral microbiota (2011)
  • Author(s): Takahashi N
  • Organizer: Harvard-Forsyth-Tohoku Research Workshop
  • Place of Presentation: Boston, USA
  • Year and Date: 2011-01-05
• [Presentation] 超個体としてのプラーク細菌叢とその機能異常としてのう蝕と歯周炎 (2010)
  • Author(s): 高橋信博
  • Organizer: 口腔感染症フォーラム2010
  • Place of Presentation: 鶴見
  • Year and Date: 2010-12-19
• [Presentation] A metabolic approach to oral microbial ecosystem in health and disease (2010)
  • Author(s): Takahashi N
  • Organizer: KADR
  • Place of Presentation: Seoul, Korea, (2010 Program and Abstract, Special Lecture 2, p. 17, 2010)
  • Year and Date: 2010-11-25
• [Presentation] プラークバイオフィルムのメタボローム解析 -糖代謝からアミノ酸代謝まで-Metabolome analysis of oral plaque biofilm -sugar metabolism and amino acid metabolism- (2010)
  • Author(s): 鷲尾純平, 真柳弦, 高橋信博
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京(J Oral Biosci 52(S): 135, 2010. (Abstract #P-38).)
  • Year and Date: 2010-09-21
• [Presentation] Metabolome analysis of glucose fermentation by dental plaque using CE-TOFMS (2010)
  • Author(s): Washio J, Mayanagi G, Katsuda Y, Hata T, Sakurada K, Sato K, Tsuji N, Takahashi N
  • Organizer: The 88th IADR
  • Place of Presentation: Barcelona, Spain, (J Dent Res 89(Special Issue B): 3382, 2010)
  • Year and Date: 2010-07-16
  • Invited
• [Book] デンタルカリエス-その病態と臨床マネージメント 原著第2版(Dental Caries -The Disease and its Clinical Management (2013)
  • Author(s): 高橋信博, 恵比須繁之(監訳)
  • Total Pages: 560
  • Publisher: 医歯薬出版, 東京
• [Book] Metabolomic approach to oral microbiota. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Takahashi N, Washio J, Mayanagi G
  • Total Pages: 334-340
  • Publisher: Springer, New York
• [Book] Metabolome analysis of oral plaque biofilm using CE-TOFMS. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Washio J, Mayanagi G, Takahashi N
  • Total Pages: 218-220
  • Publisher: Springer, New York
• [Book] Quantification and identification of bacteria in the maxillary obturator-prostheses. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Takeuchi Y, Nakajo K, Sato T, Sakuma Y, Koyama S, Sasaki K, Takahashi N
  • Total Pages: 209-211
  • Publisher: Springer, New York
• [Book] A high-sensitive alamarBlue[〇!R] method for evaluating bacterial adhesion to biomaterials. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Sakuma Y, Washio J, Takeuchi Y, Sasaki K, Takahashi N
  • Total Pages: 201-203
  • Publisher: Springer, New York
• [Book] Acid-tolerance and endogenous acid-production of oral Bifidobacteria. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Nakajo K, Beighton D, Takahashi N
  • Total Pages: 195-197
  • Publisher: Springer, New York
• [Book] Evaluation of pH at the interface between bacteria and restorative materials. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Mayanagi G, Igarashi K, Washio J, Nakajo K, Domon-Tawaraya H, Takahashi N
  • Total Pages: 192-194
  • Publisher: Springer, New York
• [Book] Actinomyces acid production: Effects on bicarbonate and fluoride at neural and acid pH. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Kawashima J, N
  • Total Pages: 189-191
  • Publisher: Springer, New York
• [Book] Silent aspiration of oral bacteria - Microbiological analysis of intraoperative bronchial fluids from patients with pulmonary carcinoma. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Hasegawa A, Sato T, Hoshikawa Y, Kondo T, Takahashi N
  • Total Pages: 181-182
  • Publisher: Springer, New York
• [Book] Divalent cations enhance short-time fluoride exposure-induced inhibition on acid production by oral streptococci. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Domon-Tawaraya H, Nakajo K, Washio J, Fukumoto S, Takahashi N
  • Total Pages: 178-180
  • Publisher: Springer, New York
• [Book] Subgingival plaque biofilm microflora of elderly subjects: quantitative analysis of Porphyromonas gingivalis and genotyping of its virulence-associated fimA. Interface Oral Health Science 2011(In: K. Sasaki, O. Suzuki, N. Takahashi (eds.)) (2012)
  • Author(s): Abiko Y, Sato T, Sakashita R, Takahashi N
  • Total Pages: 176-177
  • Publisher: Springer, New York