Microbiomes of the Normal Middle Ear and Ears With Chronic Otitis Media

• Project/Area Number: 16K11205
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: 独立行政法人国立病院機構(東京医療センター臨床研究センター)
• Principal Investigator: Minami Shujiro 独立行政法人国立病院機構(東京医療センター臨床研究センター), その他部局等, 医師 (00399544)
• Research Collaborator: Mutai Hideki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 中耳細菌叢 / メタゲノム / 16S rRNA / 慢性中耳炎 / 乳突蜂巣発育 / 耳管機能 / 中耳常在菌叢 / メタゲノム解析 / 微生物

Outline of Final Research Achievements

The human body is colonized by a wide variety of microorganisms. It was realized that most of these microorganisms cannot be grown under laboratory conditions. Recent advances in Next-Generation Sequencing technologies have provided new tools for characterizing the highly complex microbial communities that colonize various sites of the human body. The aim of this study was to profile and compare the middle ear microbiomes of human subjects with and without chronic otitis media. All consecutive patients undergoing tympanoplasty surgery for chronic otitis media or ear surgery for conditions other than otitis media were recruited. Sterile swab samples were collected from the middle ear mucosa during surgery. The human middle ear is inhabited by more diverse microbial communities than was previously thought. Alteration of the middle ear microbiome may contribute to the pathogenesis of chronic otitis media with active inflammation.

Academic Significance and Societal Importance of the Research Achievements

本研究の目的1は世界で初めて人の中耳常在菌叢を明らかにすることである。目的2は慢性中耳炎の患者を対象に中耳細菌叢を明らかにすることである。中耳に炎症の無い耳科手術（人工内耳手術など)を行った66症例からと、慢性中耳炎患者88例より手術時に中耳スワブサンプルを採取し、16S rRNA メタゲノム解析を 完了し た。正常な中耳の粘膜表面上の最も豊富な細菌門は、Proteobacteriaであった。慢性中耳炎では、Firmicutesの割合が高かった。人間の中耳は、これまで考えられていたよりも多くの細菌種が存在することが明らかになり、また細菌叢の変化が、活動性中耳炎と関連していることを明らかにした。

Research Products

• [Journal Article] A clinical and genetic study of 16 Japanese families with Waardenburg syndrome. (2019)
  • Author(s): Minami SB, Nara K, Mutai H, Morimoto N, Sakamoto H, Takiguchi T, Kaga K, Matsunaga T.
  • Journal Title: Gene Volume: 704 Pages: 86-90
  • DOI: 10.1016/j.gene.2019.04.023
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of vestibular ocular reflex and gross motor function in infants with common cavity as a type of inner ear malformation (2019)
  • Author(s): Kaga K, Kimura Y, Minami S
  • Journal Title: Acta Otolaryngologica Volume: 139 Issue: 4 Pages: 361-366
  • DOI: 10.1080/00016489.2018.1548777
  • Peer Reviewed
• [Journal Article] Elongated EABR wave latencies observed in patients with auditory neuropathy caused by OTOF mutation. (2018)
  • Author(s): Hosoya M, Minami SB, Enomoto C, Matsunaga T, Kaga K.
  • Journal Title: Laryngoscope Investig Otolaryngol. Volume: 3 Issue: 5 Pages: 388-393
  • DOI: 10.1002/lio2.210
  • Peer Reviewed / Open Access
• [Journal Article] CアームX線透視下での人工内耳電極挿入術 (2018)
  • Author(s): 南 修司郎, 山本 修子, 加我 君孝
  • Journal Title: 頭頸部外科 Volume: 28 Pages: 245-248
  • NAID: 130007510126
  • Peer Reviewed
• [Journal Article] Auditory Related Resting State fMRI Functional Connectivity in Tinnitus Patients: Tinnitus Diagnosis Performance. (2018)
  • Author(s): Minami SB, Oishi N, Watabe T, Uno K, Ogawa K
  • Journal Title: Otol Neurotol. Volume: 39 Issue: 1 Pages: 1-5
  • DOI: 10.1097/mao.0000000000001626
  • Peer Reviewed
• [Journal Article] Z形成術を用いた外耳道入口部拡大法 (2018)
  • Author(s): 南 修司郎, 山本 修子
  • Journal Title: 頭頸部外科 Volume: 27 Pages: 395-397
  • NAID: 130006496747
  • Peer Reviewed
• [Journal Article] Microbiomes of The Normal Middle Ear and Chronic Otitis Media (2017)
  • Author(s): Shujiro B. Minami, Hideki Mutai, Tomoko Suzuki Arata Horii, Naoki Oishi, Koichiro Wasano, Motoyasu Katsura, Fujinobu Tanaka, Tetsuya Takiguchi, Masato Fujii, Kimitaka Kaga
  • Journal Title: Laryngoscope Volume: 印刷中 Issue: 10
  • DOI: 10.1002/lary.26579
  • Peer Reviewed
• [Journal Article] A case of descending mediastinitis caused by Streptococcus pyogenes harboring genotype emm 25 and sequence type 660 (2017)
  • Author(s): Hiroaki Ohya, Nobuaki Mori, Takashi Takahashi, et al.
  • Journal Title: J Infect Chemother Volume: 23 Issue: 6 Pages: 403-406
  • DOI: 10.1016/j.jiac.2016.12.018
  • Peer Reviewed
• [Journal Article] Effects of vestibular rehabilitation combined with transcranial cerebellar direct current stimulation in patients with chronic dizziness: An exploratory study. (2017)
  • Author(s): Koganemaru S, Goto F, Arai M, Toshikuni K, Hosoya M, Wakabayashi T, Yamamoto N, Minami S, Ikeda S, Ikoma K, Mima T.
  • Journal Title: Brain Stimulation Volume: - Issue: 3 Pages: 576-578
  • DOI: 10.1016/j.brs.2017.02.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 当医療センターで初回人工内耳手術を行った聴覚障害児138児の療育先及びその後の就学状況調査 (2017)
  • Author(s): 南 修司郎、榎本 千江子、加藤 秀敏、山本 修子、細谷 誠、若林 毅、利國 桂太郎、松永 達雄、加我 君孝
  • Journal Title: 耳鼻咽喉科・頭頸部外科 Volume: 89 Pages: 265-269
  • Peer Reviewed
• [Journal Article] Clinical characteristics of a Japanese family with hearing loss accompanied by compound heterozygous mutations in LOXHD1. (2016)
  • Author(s): Minami SB, Mutai H, Namba K, Sakamoto H, Matsunaga T.
  • Journal Title: Auris Nasus Larynx. Volume: 43 Pages: 609-613
  • NAID: 130005773901
  • Peer Reviewed
• [Presentation] Open cavity症例に対する人工内耳手術の工夫 ～外耳道閉鎖とPalva flapの利用～. (2019)
  • Author(s): 南修司郎、山本修子、和佐野浩一郎、伊藤文展、遠藤理奈子、橋本陽介、石川直明、加我君孝.
  • Organizer: 第29回頭頸外科学会総会ならびに学術講演会
• [Presentation] Cochlear implantation in inner ear malformations. Oto-Symposium 1 - Current issue in cochlear implantation. (2018)
  • Author(s): Shujiro Minami, Nobuko Yamamoto, Kimitaka Kaga
  • Organizer: The 17th Korea-Japan Joint Meeting of Otorhinolaryngology-Head and Neck Surgery
  • Int'l Joint Research / Invited
• [Presentation] Auditory Related Resting State fMRI Functional Connectivity in Tinnitus Patients: Tinnitus Diagnosis Performance. (2018)
  • Author(s): Shujiro Minami
  • Organizer: the 6th East Asian Symposium on Otology
  • Int'l Joint Research / Invited
• [Presentation] Electrically evoked auditory brainstem responses in cochlear implantation. (2018)
  • Author(s): Shujiro Minami.
  • Organizer: the 1st Japan-Korea Scientific Meeting.
  • Int'l Joint Research / Invited
• [Presentation] 人工内耳手術を行った内耳奇形60症例の検討 (2018)
  • Author(s): 南 修司郎, 山本 修子, 加我 君孝.
  • Organizer: 第28回日本耳科学会総会・学術講演会,
• [Presentation] Microbiomes of the Normal Middle Ear and Ears with Chronic Otitis Media (2017)
  • Author(s): Shujiro B. Minami, Hideki Mutai, Arata Horii, Naoki Oishi, Koichiro Wasano, Kimitaka Kaga
  • Organizer: AAO-HNSF 2017 Annual Meeting
  • Int'l Joint Research
• [Presentation] Auditory and non-auditory resting-state functional connectivity in normal-hearing individuals with and without tinnitus: RsFMRI study (2017)
  • Author(s): Minami S.B., Oishi N., Watabe T., Uno K., Ogawa K
  • Organizer: 1st World Tinnitus Congress XII International Tinnitus Seminar
  • Int'l Joint Research
• [Presentation] Clinical and Genetic Studies of 21 families with Japanese Waardenburg Syndrome (2017)
  • Author(s): Shujiro B. Minami, Kiyomitsu Nara, Hideki Mutai, Kimitaka Kaga, Tatsuo Matsunaga
  • Organizer: IFOS Paris 2017 - the ENT World Congress
  • Int'l Joint Research
• [Presentation] RETROFACIAL APPROACH TO ACCESS THE ROUND WINDOW FOR COCHLEAR IMPLANTATION IN PATIENTS WITH MICROTIA AND AURAL ATRESIA (2017)
  • Author(s): Shujiro Minami,Nobuko Yamamoto, Kimitaka Kaga
  • Organizer: 11th Asia Pacific Symposium on Cochlear Implants and Related Sciences
  • Int'l Joint Research
• [Presentation] Ninja techniques in cochlear implant surgery (2017)
  • Author(s): Shujiro Minami, Hideki Takegoshi, Nobuko Yamamoto, Kimitaka Kaga
  • Organizer: The 9th Siebold Memorial Symposium on Hearing Implants in Yokohama
  • Int'l Joint Research / Invited
• [Presentation] 聴覚障害の画像診断と聴覚機能検査 難聴性と無難聴性耳鳴の安静時fMRI機能的結合の検討 (2016)
  • Author(s): 南 修司郎, 大石 直樹, 小川 郁
  • Organizer: 第61回日本聴覚医学会総会・学術講演会
  • Place of Presentation: 盛岡
  • Year and Date: 2016-10-20
• [Presentation] Auditory neuropathy spectrum disorder3児の人工内耳EABR波形の検討 (2016)
  • Author(s): 南 修司郎, 山本 修子, 細谷 誠, 松永 達雄, 加我 君孝
  • Organizer: 第26回日本耳科学会総会・学術講演会
  • Place of Presentation: 長野
  • Year and Date: 2016-10-06
• [Presentation] 耳鼻科Drの処方意図教えます！ (2016)
  • Author(s): 南修司郎
  • Organizer: 世田谷薬剤師会保険薬局部会9月(第118回)度勉強会
  • Place of Presentation: 世田谷区
  • Invited
• [Book] Cochlear Implantation in Children with Inner Ear Malformation and Cochlear Nerve Deficiency (2017)
  • Author(s): Shujiro Minami, Kimitaka Kaga
  • Total Pages: 169
  • Publisher: Springer
  • ISBN: 9789811013997
• [Book] EABR of Inner Ear Malformation and Cochlear Nerve Deficiency After Cochlear Implantation in Children (2016)
  • Author(s): Shujiro Minami, Kimitaka Kaga
  • Total Pages: 169
  • Publisher: Springer Singapore