Fungal mycobiome in eosinophilic chronic rhinosinusitis

• Project/Area Number: 20K22998
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: University of Fukui
• Principal Investigator: Kidoguchi Masanori 福井大学, 学術研究院医学系部門(附属病院部), 特命助教 (30880132)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 好酸球性副鼻腔炎 / 慢性副鼻腔炎 / マイクロバイオーム / 真菌

Outline of Research at the Start

好酸球性副鼻腔炎は嗅覚障害や気管支喘息の合併率が高く、鼻腔内にポリープ（鼻茸）が多発し再発率が高い難治性疾患であり、原因としては未だ不明な点が多い。申請者は、環境的な要因のひとつとして細菌叢のマイクロバイームに着目し研究を行ってきた。本研究では、好酸球性副鼻腔炎における真菌叢マイクロバイオーム解析を行い、病態解明につなげることを目的とする。具体的には、好酸球性副鼻腔炎の鼻腔に存在する真菌叢のマイクロバイオームを網羅的に同定し、すでに研究成果として得られている細菌叢のマイクロバイオームと統合することにより、好酸球性副鼻腔炎の病態に関与する微生物叢（細菌叢・真菌叢）を明らかにする。

Outline of Final Research Achievements

Nasal swab samples were collected from 179 patients with chronic rhinosinusitis (eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (non-ECRS)). The microbial DNA was extracted from the samples. The amplified sequences were measured by a next-generation sequencer using primers that amplify the internal transcribed spacer (ITS) region, and phylogenetic classification was performed. The fungal mycobiome of ECRS and non-ECRS were compared and analyzed for diversity and fungal species. It was found that certain fungal species was decreased as the severity of ECRS was increased.

Academic Significance and Societal Importance of the Research Achievements

好酸球性副鼻腔炎は嗅覚障害や気管支喘息の合併率が高く、鼻腔内にポリープ(鼻茸)が多発し再発率が高い難治性疾患であり、原因としては未だ不明な点が多い。本研究では、好酸球性副鼻腔炎における真菌叢マイクロバイオーム解析を行い、好酸球性副鼻腔炎に特徴的な真菌叢を明らかにした。本研究で見出した特定の真菌をターゲットとして新たな治療法の確立が期待される結果となった。

Research Products

• [Journal Article] Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis (2022)
  • Author(s): Imoto Yoshimasa、Ueki Shigeharu、Kato Yukinori、Yoshida Kanako、Morikawa Taiyo、Kimura Yukihiro、Kidoguchi Masanori、Tsutsumiuchi Toshiki、Koyama Keisuke、Adachi Naoto、Ito Yumi、Ogi Kazuhiro、Sakashita Masafumi、Yamada Takechiyo、Schleimer Robert P.、Takabayashi Tetsuji、Fujieda Shigeharu
  • Journal Title: Frontiers in Pharmacology Volume: 12 Pages: 793607-793607
  • DOI: 10.3389/fphar.2021.793607
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HLA‐DPB1*05:01 genotype is associated with poor response to sublingual immunotherapy for Japanese cedar pollinosis (2022)
  • Author(s): Kidoguchi Masanori、Morii Wataru、Noguchi Emiko、Yuta Atsushi、Ogawa Yukiko、Nakamura Takako、Kikuoka Hirotaka、Kouzaki Hideaki、Arai Hiroyuki、Ii Rieko、Adachi Naoto、Koyama Keisuke、Ninomiya Takahiro、Imoto Yoshimasa、Sakashita Masafumi、Fujieda Shigeharu
  • Journal Title: Allergy Volume: 77 Issue: 5 Pages: 1633-1635
  • DOI: 10.1111/all.15254
  • Peer Reviewed
• [Journal Article] Role of salivary microbiome in IL‐10 production and efficacy of sublingual immunotherapy (2021)
  • Author(s): Oka Aiko、Kidoguchi Masanori、Kariya Shin、Fujiwara Tazuko、Yuta Atsushi、Miyashita Hiromi、Higaki Takaya、Ogawa Yukiko、Kanai Kengo、Makihara Sei‐ichiro、Haruna Takenori、Kunisawa Jun、Adachi Naoto、Koyama Keisuke、Ii Rieko、Noguchi Emiko、Fujieda Shigeharu、Nishizaki Kazunori、Okano Mitsuhiro
  • Journal Title: Allergy Volume: - Issue: 8 Pages: 2617-2620
  • DOI: 10.1111/all.14858
  • Peer Reviewed / Open Access
• [Journal Article] 好酸球性副鼻腔炎の環境的要因―マイクロバイオームについて (2021)
  • Author(s): 木戸口正典
  • Journal Title: 耳鼻咽喉科・頭頸部外科 Volume: 93(1) Pages: 13-17
• [Journal Article] Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis (2020)
  • Author(s): Imoto Y, Takabayashi T, Sakashita M, Kato Y, Yoshida K, Kidoguchi M, Koyama K, Adachi N, Kimura Y, Ogi K, Ito Y, Kanno M, Okamoto M, Narita N, Fujieda S.
  • Journal Title: Biomolecules Volume: 18;10(11) Issue: 11 Pages: 1568-1568
  • DOI: 10.3390/biom10111568
  • Peer Reviewed / Open Access
• [Journal Article] Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population. (2020)
  • Author(s): Kidoguchi M, Yoshida K, Noguchi E, Nakamura T, Morii W, Haruna T, Okano M, Yamashita Y, Haruna S, Hasegawa M, Yoshida N, Ninomiya T, Imoto Y, Sakashita M, Takabayashi T, Fujieda S.
  • Journal Title: Allergology International Volume: 69(4) Issue: 4 Pages: 619-621
  • DOI: 10.1016/j.alit.2020.04.005
  • NAID: 130007926244
  • Peer Reviewed / Open Access
• [Journal Article] Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis (2020)
  • Author(s): Oka A, Ninomiya T, Fujiwara T, Takao S, Sato Y, Gion Y, Minoura A, Haruna SI, Yoshida N, Sakuma Y, Izuhara K, Ono J, Taniguchi M, Haruna T, Higaki T, Kariya S, Koyama T, Takabayashi T, Imoto Y, Sakashita M, Kidoguchi M, Nishizaki K, Fujieda S, Okano M.
  • Journal Title: Allergology International Volume: 69 Issue: 3 Pages: 417-423
  • DOI: 10.1016/j.alit.2019.12.004
  • NAID: 130007877682
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Presentation] HLA-DPB1*05:01 genotype is a predictive biomarker of sublingual immunotherapy response for Japanese cedar pollinosis (2022)
  • Author(s): Masanori Kidoguchi、Emiko Noguchi、Atsushi Yuta、Shigeharu Fujieda
  • Organizer: American Academy of Allergy Asthma & Immunology 2022 annual meeting
  • Int'l Joint Research
• [Presentation] The association between the human microbiome in the nasal cavity and the number of sensitization in allergic rhinitis. (2022)
  • Author(s): Keisuke Koyama、Masanori Kidoguchi、Naoto Adachi、Rieko Ii、Yukihiro Kimura、Kazuhiro Ogi、Masafumi Sakashita、Emiko Noguchi、Shigeharu Fujieda
  • Organizer: 18th Japan-Korea Joint Meeting of Otorhinolaryngology - Head and Neck Surgery
  • Int'l Joint Research
• [Presentation] アレルギー性鼻炎における鼻腔・唾液・便のマイクロバイオーム (2022)
  • Author(s): 小山佳祐、木戸口正典、足立直人、井伊里恵子、坂下雅文、野口恵美子、藤枝重治
  • Organizer: 第2回 耳鼻咽喉科免疫アレルギー感染症学会
• [Presentation] アレルギー性鼻炎と鼻腔マイクロバイオーム (2022)
  • Author(s): 木戸口正典
  • Organizer: 第2回 耳鼻咽喉科免疫アレルギー感染症学会
  • Invited
• [Presentation] 次世代シークエンサーを用いた好酸球性副鼻腔炎の鼻腔真菌叢解析 (2022)
  • Author(s): 足立直人、木戸口正典、井伊里恵子、小山佳祐、意元義政、坂下雅文、高林哲司、田中康広、野口恵美子、藤枝重治
  • Organizer: 第2回 耳鼻咽喉科免疫アレルギー感染症学会
• [Presentation] 好酸球性中耳炎のマイクロバイオーム解析 (2022)
  • Author(s): 井伊里恵子、足立直人、木戸口正典、野村彩美、高畑淳子、小山佳祐、宮本秀高、 廣瀬由紀、岡本昌之、野口恵美子、藤枝重治、松原篤、田渕経司
  • Organizer: 第2回 耳鼻咽喉科免疫アレルギー感染症学会
• [Presentation] HLA遺伝子多型によるスギ花粉舌下免疫療法の応答性を予測する薬理遺伝学的検討 (2021)
  • Author(s): 木戸口正典、藤枝重治
  • Organizer: 第1回 日本耳鼻咽喉科免疫アレルギー感染症学会
• [Presentation] HLA遺伝子多型による舌下免疫療法の新たな薬理遺伝学的バイオマーカー (2021)
  • Author(s): 木戸口正典
  • Organizer: 第60回 日本鼻科学会
  • Invited
• [Presentation] Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population (2021)
  • Author(s): Masanori Kidoguchi、Emiko Noguchi、Shigeharu Fujieda
  • Organizer: The 29th Congress of The European Rhinologic Society
  • Int'l Joint Research
• [Presentation] 増悪を繰り返す喉頭アレルギーに著効した舌下免疫療法の1例 (2021)
  • Author(s): 木戸口正典、足立直人、井伊里恵子、田渕経司、意元義政、坂下雅文、藤枝重治
  • Organizer: 第70回 日本アレルギー学会
• [Presentation] 鼻副鼻腔疾患と細菌叢 (2021)
  • Author(s): 藤枝重治、小山佳祐、足立直人、木戸口正典
  • Organizer: 第122回 日本耳鼻咽喉科学会総会・学術講演会
  • Invited
• [Presentation] 慢性副鼻腔炎のマイクロバイオーム解析 (2020)
  • Author(s): 木戸口正典
  • Organizer: 第8回 日本耳鼻咽喉科感染症・エアロゾル学会
  • Invited
• [Presentation] Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population (2020)
  • Author(s): Masanori Kidoguchi, Kanako Yoshida, Takako Nakamura, Wataru Morii, Takahiro Ninomiya, Yoshimasa Imoto, Masafumi Sakashita, Tetsuji Takabayashi, Emiko Noguchi, Shigeharu Fujieda
  • Organizer: JSA/WAO Joint Congress 2020
  • Int'l Joint Research
• [Presentation] NOS2遺伝子多型が鼻茸中のNOS2発現量および術後再発に与える影響 (2020)
  • Author(s): 木戸口正典、吉田加奈子、藤枝重治
  • Organizer: 第38回 日本耳鼻咽喉科免疫アレルギー学会
• [Presentation] 慢性副鼻腔炎エンドタイプ診断パネルの開発と抗モノクローナル抗体薬への応用について (2020)
  • Author(s): 木戸口正典
  • Organizer: 第59回 日本鼻科学会総会・学術講演会
  • Invited