Construction of a preventive approach for chronic lung diseases based on a maintenance of tongue microbiota

• Project/Area Number: 19H03863
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57080:Social dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Takeshita Toru 九州大学, 歯学研究院, 准教授 (50546471)
• Co-Investigator(Kenkyū-buntansha): 松元 幸一郎 九州大学, 医学研究院, 准教授 (60325462) ; 二宮 利治 九州大学, 医学研究院, 教授 (30571765) ; 古田 美智子 九州大学, 歯学研究院, 講師 (20509591)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2020: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2019: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 口腔常在微生物叢 / 舌苔 / COPD / 16S rRNA / 16S rRNA遺伝子 / 呼吸器 / マイクロバイオーム

Outline of Research at the Start

呼吸器における慢性炎症は気流制限を引き起こし重症化すれば呼吸不全から死に至る。COPDと呼ばれるこの疾患の原因は喫煙がよく知られているがその他の炎症誘発因子の特定と対策も急がれている。本研究では我々が常時大量に飲み込んでいる口腔常在微生物叢に着目し、その量や質の悪化と発症・増悪との関連を検討する。重症COPD患者と健常地域住民との舌苔微生物叢大規模比較解析からCOPD関連微生物叢パターンを解明するとともに、微生物叢管理法の構築を目指し唾液中の微生物叢制御成分を特定する。本研究の結果は舌苔微生物叢管理という全く新たな視点からの慢性呼吸器疾患予防アプローチの構築にむけた重要な礎となる。

Outline of Final Research Achievements

This study investigated a relationship between chronic obstructive pulmonary disease and tongue microbiota by using a comprehensive molecular approach analyzing bacterial DNA. A molecular epidemiological study for community-dwelling elderly adults demonstrated that a high-biomass tongue microbiota was significantly associated with airflow limitation which is a primary symptom of chronic obstructive pulmonary disease, after adjustment for smoking intensity and other covariates. Of the predominant commensals, a higher amount of Prevotella melaninogenica was associated with a higher prevalence of airflow limitation. Our results indicate that dysbiotic tongue microbiota is associated with a higher prevalence of airflow limitation.

Academic Significance and Societal Importance of the Research Achievements

我々は口腔内表面から剥がれ落ちた大量の常在細菌を唾液とともに常時飲み込んでいる。これらの細菌の一部が微量ながら気道にも流入していることが近年明らかとなってきた。本研究ではこうして微小誤嚥される口腔微生物の主要な供給源である舌苔微生物叢の量および組成と肺機能との関連の存在を明らかにした。本研究により口腔管理による舌の常在細菌叢の制御が肺の健康維持に役立つ可能性が示された。

Research Products

• [Journal Article] High-Level Acquisition of Maternal Oral Bacteria in Formula-Fed Infant Oral Microbiota (2022)
  • Author(s): Kageyama Shinya、Furuta Michiko、Takeshita Toru、Ma Jiale、Asakawa Mikari、Yamashita Yoshihisa
  • Journal Title: mBio Volume: 13 Issue: 1
  • DOI: 10.1128/mbio.03452-21
  • Peer Reviewed / Open Access
• [Journal Article] Risk Prediction Model for Incident Atrial Fibrillation in a General Japanese Population ― The Hisayama Study ― (2021)
  • Author(s): Hata Jun、Nagata Takuya、Sakata Satoko、Oishi Emi、Furuta Yoshihiko、Hirakawa Yoichiro、Honda Takanori、Yoshida Daigo、Kitazono Takanari、Ninomiya Toshiharu
  • Journal Title: Circulation Journal Volume: 85 Issue: 8 Pages: 1373-1382
  • DOI: 10.1253/circj.CJ-20-0794
  • NAID: 130008066724
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2021-07-21
  • Peer Reviewed / Open Access
• [Journal Article] Airflow limitation and tongue microbiota in community-dwelling elderly individuals (2021)
  • Author(s): Takeshita Toru、Matsumoto Koichiro、Furuta Michiko、Fukuyama Satoru、Takeuchi Kenji、Ogata Hiroaki、Asakawa Mikari、Kageyama Shinya、Hata Jun、Ninomiya Toshiharu、Inoue Hiromasa、Yamashita Yoshihisa
  • Journal Title: ERJ Open Research Volume: － Issue: 2 Pages: 00616-2020
  • DOI: 10.1183/23120541.00616-2020
  • Peer Reviewed / Open Access
• [Journal Article] Tongue Microbiota Composition and Dental Caries Experience in Primary School Children (2021)
  • Author(s): Zhang Daixi、Takeshita Toru、Furuta Michiko、Kageyama Shinya、Asakawa Mikari、Nambu Koki、Yamashita Yoshihisa
  • Journal Title: mSphere Volume: 6 Issue: 2
  • DOI: 10.1128/msphere.01252-20
  • Peer Reviewed / Open Access
• [Journal Article] Development of a risk prediction model for incident hypertension in Japanese individuals: the Hisayama Study (2021)
  • Author(s): Oishi, Emi; Hata, Jun; Honda, Takanori; Sakata, Satoko; Chen, Sanmei; Hirakawa, Yoichiro; Yoshida, Daigo; Shibata, Mao; Ohara, Tomoyuki; Furuta, Yoshihiko;
  • Journal Title: Hypertension Research Volume: 44 Issue: 9 Pages: 1221-1229
  • DOI: 10.1038/s41440-021-00673-7
  • Peer Reviewed
• [Journal Article] Serum NT-proBNP levels and histopathological myocardial fibrosis in autopsied cases from a Japanese community: The Hisayama Study (2021)
  • Author(s): Sasaki Takaya、Izumaru Kensuke、Hata Jun、Sakata Satoko、Oishi Emi、Nagata Takuya、Tsuboi Nobuo、Oda Yoshinao、Kitazono Takanari、Yokoo Takashi、Ninomiya Toshiharu
  • Journal Title: Journal of Cardiology Volume: 78 Issue: 3 Pages: 237-243
  • DOI: 10.1016/j.jjcc.2021.03.014
  • Peer Reviewed / Open Access
• [Journal Article] Midlife and late-life diabetes and sarcopenia in a general older Japanese population: the Hisayama Study (2021)
  • Author(s): Kimitaka Nakamura, Daigo Yoshida, Takanori Honda, Jun Hata, Mao Shibata, Yoichiro Hirakawa, Yoshihiko Furuta, Hiro Kishimoto, Tomoyuki Ohara, Sanmei Chen, Takanari Kitazono, Yasuharu Nakashima, Toshiharu Ninomiya
  • Journal Title: J Diabetes Investig Volume: in press Issue: 10 Pages: 1-26
  • DOI: 10.1111/jdi.13550
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Urinary N-terminal pro?B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study (2021)
  • Author(s): Yamasaki, Keisuke; Hata, Jun; Ide, Tomomi; Nagata, Takuya; Sakata, Satoko; Yoshida, Daigo; Honda, Takanori; Hirakawa, Yoichiro; Nakano, Toshiaki; Kitazono, Takanari;
  • Journal Title: Environmental health and preventive medicine Volume: 26 Issue: 1 Pages: 44571-44571
  • DOI: 10.1186/s12199-021-00970-0
  • NAID: 210000158976
  • Peer Reviewed / Open Access
• [Journal Article] Clinical utility of subgingival plaque-specific bacteria in salivary microbiota for detecting periodontitis (2021)
  • Author(s): Ma Jiale、Kageyama Shinya、Takeshita Toru、Shibata Yukie、Furuta Michiko、Asakawa Mikari、Yamashita Yoshihisa
  • Journal Title: PLOS ONE Volume: 16 Issue: 6 Pages: e0253502-e0253502
  • DOI: 10.1371/journal.pone.0253502
  • Peer Reviewed / Open Access
• [Journal Article] Current status of the certification of long-term care insurance among individuals with dementia in a Japanese community: The Hisayama Study (2021)
  • Author(s): Ohara, Tomoyuki; Yoshida, Daigo; Hata, Jun; Shibata, Mao; Honda, Takanori; Furuta, Yoshihiko; Hirabayashi, Naoki; Kitazono, Takanari; Nakao, Tomohiro; Ninomiya, Toshiharu;
  • Journal Title: Psychiatry and clinical neurosciences Volume: - Issue: 5 Pages: 182-182
  • DOI: 10.1111/pcn.13204
  • Peer Reviewed / Open Access
• [Journal Article] Compositional Shift of Oral Microbiota Following Surgical Resection of Tongue Cancer (2020)
  • Author(s): Kageyama Shinya、Nagao Yuka、Ma Jiale、Asakawa Mikari、Yoshida Ryoji、Takeshita Toru、Hirosue Akiyuki、Yamashita Yoshihisa、Nakayama Hideki
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 10 Pages: 60084-60084
  • DOI: 10.3389/fcimb.2020.600884
  • Peer Reviewed / Open Access
• [Journal Article] Influence of the accumulation of unhealthy eating habits on obesity in a general Japanese population: the Hisayama Study. (2020)
  • Author(s): Ishida Y, Yoshida D, Honda T, Hirakawa Y, Shibata M, Sakata S, Furuta Y, Oishi E, Hata J, Kitazozno T, Ninomiya T
  • Journal Title: Nutrients Volume: 12 Issue: 10 Pages: 3160-3160
  • DOI: 10.3390/nu12103160
  • Peer Reviewed / Open Access
• [Journal Article] Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation (2020)
  • Author(s): Oku Saori、Takeshita Toru、Futatsuki Toshiko、Kageyama Shinya、Asakawa Mikari、Mori Yasuo、Miyamoto Toshihiro、Hata Jun、Ninomiya Toshiharu、Kashiwazaki Haruhiko、Yamashita Yoshihisa
  • Journal Title: PLOS Pathogens Volume: 16 Issue: 3 Pages: e1008348-e1008348
  • DOI: 10.1371/journal.ppat.1008348
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Initial Colonizing Bacteria in Dental Plaques from Young Adults Using Full-Length 16S rRNA Gene Sequencing (2019)
  • Author(s): Ihara Yukari、Takeshita Toru、Kageyama Shinya、Matsumi Rie、Asakawa Mikari、Shibata Yukie、Sugiura Yuki、Ishikawa Kunio、Takahashi Ichiro、Yamashita Yoshihisa
  • Journal Title: mSystems Volume: 4 Issue: 5
  • DOI: 10.1128/msystems.00360-19
  • Peer Reviewed / Open Access
• [Presentation] 口腔常在微生物叢の正常像と疾患との関連 (2021)
  • Author(s): 竹下徹
  • Organizer: 第48回日本毒性学会学術大会
  • Invited
• [Presentation] 口腔マイクロバイオームと口腔および全身の健康 (2021)
  • Author(s): 竹下徹
  • Organizer: フォーサム2021
  • Invited
• [Presentation] 口腔常在微生物叢の構成と嚥下性肺炎のリスク (2020)
  • Author(s): 竹下徹
  • Organizer: 第68回日本化学療法学会総会
  • Invited
• [Presentation] 我々が飲み込んでいる口腔常在微生物叢の構成と健康状態との関連 (2020)
  • Author(s): 竹下徹
  • Organizer: 第62回歯科基礎医学会総会
  • Invited
• [Presentation] Bacterial composition of overall oral microbiota associated with periodontal disease and health. (2020)
  • Author(s): 竹下徹
  • Organizer: 第68回国際歯科研究学会日本部会（JADR）総会・学術大会
  • Invited
• [Presentation] 口腔常在微生物の構成と健康との関連 (2019)
  • Author(s): 竹下徹
  • Organizer: プロバイオティクスシンポジウム19
  • Invited
• [Presentation] 新たな健康増進アプローチの開発に向けた口腔常在微生物叢の理解 (2019)
  • Author(s): 竹下徹
  • Organizer: 第29回九州臨床再生歯科研究会学術講演会
  • Invited