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Mechanisms of Vaginal Homeostasis by Vaginal Bacterial Flora

Research Project

Project/Area Number 20K18177
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

TAKADA Kazuhide  日本大学, 医学部, 助教 (60848711)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords腟細菌叢 / 子宮内細菌叢 / Lactobacillus / 膣内細菌叢 / 抗菌ペプチド / FRT-organ axes / 腟内細菌叢 / 乳酸桿菌 / 腟上皮細胞 / 上皮バリア機能 / プロバイオティクス
Outline of Research at the Start

健常人の腟内細菌叢は乳酸桿菌主体であることが多い。腟内細菌叢の乱れ(dysbiosis)は、性感染症や早産等のリスクを高めるため、乳酸桿菌を用いたプロバイオティクスが試みられている。本研究では乳酸桿菌同士の増殖阻害作用や、腟上皮バリア機能と各菌種との相互作用を検討することで、腟細菌叢による腟内恒常性維持機構を明らかにする。またその結果、より腟内に定着しやすく、性感染症予防に効果的な菌種を選定する評価項目の確立も期待できる。

Outline of Final Research Achievements

Bacterial flora in the female reproductive organs plays an important role in homeostasis. When culture supernatants of Lactobacillus strains, mainly vaginally derived, were added to each other, almost no significant changes in bacterial growth were observed. This suggests that the mechanism by which the vaginal flora becomes Lactobacillus-dominated may be due to host selection pressure rather than competition among the bacteria. Culture supernatants of Gardnerella vaginalis also significantly enhanced the secretion of the antimicrobial peptide Elafin from cervical epithelial cells. In the endometrial flora, viable L. crispatus and culture supernatants significantly promoted trophoblast invasion, which may affect implantation.

Academic Significance and Societal Importance of the Research Achievements

腟内細菌叢の乱れは、細菌性腟症など様々な原因となる。治療法の一つとしてプロバイオティクスがあるが、どの菌種がどのような機序で作用しているか、また組織に定着しているかは不明な点が多い。そのため、理想的とされるLactobacillus主体の細菌叢はどのようなメカニズムで維持されるのか、また病原菌はどのような影響を粘膜免疫に及ぼすかの一端を明らかにした本研究は、この分野の理解促進につながる。また子宮内細菌叢は健常人の菌種構成すらコンセンサスに至っておらず、今回の研究成果は子宮内細菌叢の役割の理解および、将来の適切な細菌叢介入手段の検討に寄与する。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (23 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (2 results)

  • [Int'l Joint Research] Gabrichevsky Research Institute(ロシア連邦)

    • Related Report
      2022 Research-status Report
  • [Journal Article] 合併増大号 今月の臨床 産婦人科医のための感染症最新レクチャー 総論 女性生殖器の常在菌と粘膜免疫2024

    • Author(s)
      髙田 和秀, 相澤(小峯)志保子, 早川 智
    • Journal Title

      臨床婦人科産科

      Volume: 78 Issue: 1 Pages: 12-21

    • DOI

      10.11477/mf.1409211124

    • ISSN
      0386-9865, 1882-1294
    • Year and Date
      2024-01-10
    • Related Report
      2023 Annual Research Report
  • [Journal Article] 妊娠時の腸内細菌叢はどこまでわっているか2023

    • Author(s)
      髙田和秀, 相澤(小峯) 志保子, 早川 智
    • Journal Title

      周産期医学

      Volume: 53 増刊号 Pages: 21-23

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Pathological roles of antimicrobial peptides and pro-inflammatory factors secreted from the cervical epithelium in Gardnerella vaginalis-abundant vaginal flora in pregnancy2023

    • Author(s)
      Matsuda E, Takada K, Kobayashi O, Nakajima T, Ikeda Y, Asai-Sato M, Kawakami K, Komatsu A, Chishima F, Komine-Aizawa S, Hayakawa S, Kawana K.
    • Journal Title

      Journal of Reproductive Immunology

      Volume: 156 Pages: 103797-103797

    • DOI

      10.1016/j.jri.2023.103797

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Female reproductive tract-organ axes2023

    • Author(s)
      Kazuhide Takada, Vyacheslav G. Melnikov, Ryoki Kobayashi, Shihoko Komine-Aizawa, Noriko M. Tsuji. Satoshi Hayakawa
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 111001-111001

    • DOI

      10.3389/fimmu.2023.1110001

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] How were Lactobacillus species selected as single dominant species in the human vaginal microbiota? Coevolution of humans and Lactobacillus2022

    • Author(s)
      Shingo Hayashida, Kazuhide Takada, Vyacheslav G. Melnikov, Shihoko Komine-Aizawa, Noriko M. Tsuji, Satoshi Hayakawa
    • Journal Title

      Medical Hypotheses

      Volume: 163 Pages: 110858-110858

    • DOI

      10.1016/j.mehy.2022.110858

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lactobacillus crispatus promotes invasion of the HTR-8/SVneo trophoblast2021

    • Author(s)
      Yoshida T, Takada K, Komine-Aizawa S, Kamei Y, Ishihara O, Hayakawa S.
    • Journal Title

      Placenta

      Volume: 111 Pages: 76-81

    • DOI

      10.1016/j.placenta.2021.06.006

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of endometrial microbiota on immune tolerance at the maternal-fetal interface2024

    • Author(s)
      Kazuhide Takada, Jonghyun Bae, Quang Duy Trinh, Shihoko Komine-Aizawa, Dong Wook Kim,Satoshi Hayakawa
    • Organizer
      米国生殖免疫学会(ASRI2024)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 子宮内細菌叢がmaternal-fetal interfaceにおける免疫寛容機序に与える影響の研究2023

    • Author(s)
      髙田和秀, Jonghyun Bae, Quang Duy Trinh, 相澤(小峯) 志保子, 早川 智
    • Organizer
      第31回日本胎盤学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 女性生殖器の常在菌と粘膜免疫(シンポジウム:ヒトの生殖と免疫 )2023

    • Author(s)
      髙田和秀
    • Organizer
      第68回日本生殖医学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 子宮内細菌叢がmaternal-fetal interfaceにおける免疫寛容機序に与える影響の研究2023

    • Author(s)
      髙田和秀, Jonghyun Bae, Quang Duy Trinh, 相澤(小峯)志保子, Dong Wook Kim, 早川 智
    • Organizer
      第38回日本生殖免疫学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細菌性腟症原因菌と腟常在菌が子宮頸管上皮細胞の抗菌ペプチド産生に及ぼす影響2021

    • Author(s)
      松田恵里那,高田和秀,相澤(小峯)志保子, 川名 敬,早川 智
    • Organizer
      第37回日本産婦人科感染症学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Lactobacillus crispatusは他の乳酸桿菌種からの増殖抑制を受けにくい2021

    • Author(s)
      林田慎吾、髙田和秀、相澤(小峯)志保子、早川智
    • Organizer
      第37回日本産婦人科感染症学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 腸-腟相関 ~世代を超える細菌叢~2021

    • Author(s)
      髙田和秀
    • Organizer
      第24回日本臨床腸内微生物学会総会・学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Lactobacillus acidophilusはretinoic acid存在 下でTHP-1細胞からのIL-10産生を促進する2021

    • Author(s)
      並木貴宏,高田和秀,高野智圭, 相澤志保子,早川 智
    • Organizer
      第49回日本臨床免疫学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Lactobacillus crispatusは不死化絨毛細胞株HTR/SVneoの浸潤を促進するがGardnerella vaginalisは抑制する2021

    • Author(s)
      髙田和秀、吉田智昭、相澤(小峯)志保子、亀井良政、石原 理、早川 智
    • Organizer
      第36回日本生殖免疫学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 細菌性腟症原因菌と腟常在菌が子宮頸管上皮細胞の抗菌ペプチド産生に及ぼす影響2021

    • Author(s)
      松田恵理那、髙田和秀、相澤(小峯)志保子、早川 智、川名 敬
    • Organizer
      第36回日本生殖免疫学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒト不死化腟上皮細胞におけるIL-33とthymic stromal lymphopoietin(TSLP)産生の検討2020

    • Author(s)
      高田和秀,相澤(小峯)志保子, Trinh Duy Quang,早川 智
    • Organizer
      第48回日本臨床免疫学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 細菌性腟症原因菌と腟常在菌が子宮頸管上皮細胞の 抗菌ペプチド産生に及ぼす影響2020

    • Author(s)
      松田恵里那,高田和秀,相澤志保子, 川名 敬,早川 智
    • Organizer
      第48回日本臨床免疫学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 腸管と女性生殖器のマイクロビオータ:隣どうしの誼2020

    • Author(s)
      早川 智, 髙田和秀, 高野智圭, 相澤志保子
    • Organizer
      ヤクルト・バイオサイエンス研究財団 第29回腸内フローラシンポジウム
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 女性生殖器のマイクロバイオータ2020

    • Author(s)
      早川 智,高田和秀,林田真吾, 高野智圭,相澤志保子
    • Organizer
      第48回日本臨床免疫学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] Reproductive Immunology 1st Edition, Chapter 20: Interactions between the epithelial barrier and the microbiota in the reproductive tract2021

    • Author(s)
      Takada K, Komine-Aizawa S, Tsuji NM, Hayakawa S.
    • Total Pages
      460
    • Publisher
      Academic Press
    • ISBN
      9780128185087
    • Related Report
      2020 Research-status Report
  • [Book] ヒト常在菌叢と生理機能・全身疾患, 第六章女性生殖器常在菌・感染微生物と周産期疾患2020

    • Author(s)
      髙田和秀, 早川 智
    • Total Pages
      325
    • Publisher
      シーエムシー出版
    • ISBN
      9784781315195
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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