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Development of preventive and therapeutic methods for preterm birth by vaginal microbiome profiling

Research Project

Project/Area Number 18K16822
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionFukuoka University

Principal Investigator

Urushiyama Daichi  福岡大学, 医学部, 講師 (50790028)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腟内細菌叢 / 16S rRNA遺伝子 / 絨毛膜羊膜炎 / 切迫早産 / 早産 / 機械学習 / 妊娠延長期間 / 発達障害 / 腟内細菌叢解析 / デジタルPCR / 16SrDNA / Random Forest / 子宮内感染 / 膣マイクロバイオーム / マイクロバイオームプロファイル
Outline of Final Research Achievements

By analyzing the vaginal bacterial flora, we were able to identify targets in new preventive and therapeutic strategies for preterm birth and reach the stage of advocating new therapeutic methods using antibiotics.
Specifically, by combining vaginal metagenomic analysis and machine learning, we identified 20 species of bacteria associated with chorioamnionitis (CAM) that cause preterm birth and created a new scoring method. The high-risk (PCAM) group had a significantly shorter duration of pregnancy (median difference, 13 days) and a significantly higher frequency of developmental disorders in 3-year-old infants (PCAM, 28%; non-PCAM, 4%). We also identified a combination of antibacterial agents that are presumed to be able to prevent and treat CAM.

Academic Significance and Societal Importance of the Research Achievements

妊娠婦人の子宮内感染は早産や胎児感染を引き起こします。感染を伴う早産例では、中・長期的な臓器障害を受けるリスクが高まります。本邦では、晩産化に伴うハイリスク妊娠率の増加や出生数の減少が深刻化するなかで、子宮内感染を予測し、適切に治療・管理し、一人でも多く健常な児を出生させることが強く求められています。
本研究では腟内フローラを解析することで子宮内感染のリスクを診断できることを明らかにしました。ターゲットとなる細菌群を同定でき、治療薬の候補も見つけることができました。本手法でCAMを予測し、治療することができれば、早産リスクを低減できるだけでなく、発達障害等のリスクも減らせる可能性があります。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (4 results) Book (7 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] MicroRNAs miR-4535 and miR-1915-5p in amniotic fluid as predictive biomarkers for chorioamnionitis2021

    • Author(s)
      Kiyoshima C, Shirasu N, Urushiyama D, Fukagawa S, Hirakawa T, Yoshikawa K, Izuchi D, Miyata K, Kurakazu M, Yotsumoto F, Hiromatsu K, Nomiyama M, Ohta E, Hirose S, Ogura Y, Hayashi T, Hata K, Nabeshima K, Yasunaga S, Miyamoto S
    • Journal Title

      Future Science OA

      Volume: Published online Issue: 5

    • DOI

      10.2144/fsoa-2021-0006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of Vaginal and Endometrial Microbiota Communities in Infertile Women With a History of Repeated Implantation Failure2020

    • Author(s)
      Ichiyama Takuhiko、Kuroda Keiji、Nagai Yoko、Urushiyama Daichi、Ono Motoharu、Yamaguchi Takashi、Nagayoshi Motoi、Sakuraba Yoshiyuki、Yamasaki Fumio、Hata Kenichiro、Miyamoto Shingo、Itakura Atsuo、Takeda Satoru、Tanaka Atsushi
    • Journal Title

      Reproductive Medicine and Biology

      Volume: Published online Pages: 1-25

    • DOI

      10.21203/rs.3.rs-73125/v1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The combination of maternal blood and amniotic fluid biomarkers improves the predictive accuracy of histologic chorioamnionitis2019

    • Author(s)
      Masamitsu Kurakazu, Fusanori Yotsumoto, Hisatomi Arima, Daisuke Izuchi, Daichi Urushiyama, Kohei Miyata, Chihiro Kiyoshima, Satoshi Fukagawa, Kenichi Yoshikawa, Mariko Kurakazu, Toyofumi Hirakawa, Koichi Shigekawa, Ryota Araki, Ayako Sanui, Msaharu Murata, Kazuki Nabeshima, Shingo Miyamoto
    • Journal Title

      Placenta

      Volume: 80 Pages: 4-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Predictive diagnosis of chorioamnionitis by quantification of specific vaginal bacteria using droplet digital PCR2021

    • Author(s)
      Daichi Urushiyama, Chihiro Kiyoshima, Toyofumi Hirakawa, Daisuke Izuchi, Satoshi Fukagawa, Ayako Sanui, Kohei Miyata, Masamitsu Kurakazu, Fusanori Yotsumoto, Kenichiro Hata, Shingo Miyamoto
    • Organizer
      第73回日本産科婦人科学会学術講演会、インターナショナルセッション
    • Related Report
      2020 Annual Research Report
  • [Presentation] Perinatal outcomes in patients with preterm labor diagnosed as a high-risk of chorioamnionitis by vaginal microbiome analysis2020

    • Author(s)
      Daichi Urushiyama, Chihiro Kiyoshima, Satoshi Fukagawa, Masamitsu Kurakazu, Fusanori Yotsumoto, Kenichiro Hata, Shingo Miyamoto
    • Organizer
      第72回日本産科婦人科学会学術講演会、インターナショナルセッション
    • Related Report
      2020 Annual Research Report
  • [Presentation] Perinatal outcomes in patients with preterm labor diagnosed as a high-risk of chorioamnionitis by vaginal microbiome analysis2020

    • Author(s)
      漆山大知、清島千尋、深川怜史、倉員正光、四元房典、秦健一郎、宮本新吾
    • Organizer
      第72回日本産科婦人科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腟内細菌叢解析による絨毛膜羊膜炎の予測2019

    • Author(s)
      漆山大知、平川豊文、清島千尋、井槌大介、深川怜史、倉員正光、荒木陵多、讃井絢子、四元房典、村田将春、秦健一郎、宮本新吾
    • Organizer
      第71回日本産科婦人科学会
    • Related Report
      2018 Research-status Report
  • [Book] 周産期領域における細菌叢解析で期待されることは?,No.50572021

    • Author(s)
      漆山大知
    • Total Pages
      80
    • Publisher
      日本医事新報社
    • Related Report
      2020 Annual Research Report
  • [Book] メタゲノム解析・メタ16S解析,遺伝子医学 第11巻第2号(通巻36号)2021

    • Author(s)
      漆山大知,秦健一郎,宮本新吾
    • Total Pages
      154
    • Publisher
      株式会社メディカルドゥ
    • Related Report
      2020 Annual Research Report
  • [Book] 「周産期医学」特集 周産期医療と細菌叢 妊婦編 早産と羊水細菌叢2020

    • Author(s)
      漆山大知, 秦健一郎, 宮本新吾
    • Total Pages
      400
    • Publisher
      東京医学社
    • Related Report
      2020 Annual Research Report
  • [Book] ヒトマイクロバイオームVol.2 ~解析技術の進展とデータ駆動型・ターゲット機能型研究最前線~(監修/服部正平)第5編第3章 生殖器系マイクロバイオームと疾患―女性生殖器系のマイクロバイオームと早産予防・治療を中心に―2020

    • Author(s)
      漆山大知,秦健一郎,宮本新吾
    • Total Pages
      623
    • Publisher
      株式会社エヌ・ティー・エス
    • Related Report
      2020 Annual Research Report
  • [Book] 化学工業 2020年8月号、特集 次世代健康・医療・福祉の科学、絨毛膜羊膜炎関連微生物の同定ならびに検出方法の開発2020

    • Author(s)
      漆山大知,秦健一郎,宮本新吾
    • Total Pages
      528
    • Publisher
      化学工業社
    • Related Report
      2020 Annual Research Report
  • [Book] 「周産期医学」特集 周産期医療と細菌叢 妊婦編 早産と羊水細菌叢2020

    • Author(s)
      漆山大知、秦健一郎、宮本新吾
    • Total Pages
      120
    • Publisher
      東京医学社
    • Related Report
      2019 Research-status Report
  • [Book] ヒトマイクロバイオーム Vol.22020

    • Author(s)
      漆山大知、秦健一郎、宮本新吾
    • Total Pages
      549
    • Publisher
      株式会社エヌ・ティー・エス
    • ISBN
      9784860436599
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 子宮内感染の検出法2020

    • Inventor(s)
      宮本新吾、漆山大知、四元房典、秦健一郎
    • Industrial Property Rights Holder
      宮本新吾、漆山大知、四元房典、秦健一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-013930
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 子宮内感染の検出法2020

    • Inventor(s)
      宮本新吾、漆山大知、四元房典、秦健一郎
    • Industrial Property Rights Holder
      福岡大学、国立成育医療研究センター
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 絨毛膜羊膜炎の発症予測方法2019

    • Inventor(s)
      宮本新吾、漆山大知、四元房典、秦健一郎
    • Industrial Property Rights Holder
      福岡大学、国立成育医療研究センター
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 絨毛膜羊膜炎の発症予測方法2019

    • Inventor(s)
      宮本新吾、漆山大知、四元房典、秦健一郎
    • Industrial Property Rights Holder
      福岡大学、国立成育医療研究センター
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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