Omics analysis for elucidation of pathogenic bacterial clearance mechanism of resident bacterial flora

• Project/Area Number: 15K08471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Kyorin University
• Principal Investigator: OSAKI Takako 杏林大学, 医学部, 准教授 (90255406)
• Co-Investigator(Kenkyū-buntansha): 高橋 志達 杏林大学, 医学部, 非常勤講師 (30701099)
• Research Collaborator: KAMIYA Shigeru ; YONEZAWA Haideo ; Zaman Cynthia ; HOJO Fuhito ; OKUDA Masumi ; KIKUCHI Shyogo ; LYIN Yingson
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Helicobacter pylori / 常在細菌叢 / マイクロビオータ / 胃内細菌叢 / 空腸細菌叢 / β多様性解析 / ヘリコバクター・ピロリ / マイクロバイオ―タ / 多様性比較 / スナネズミ / 連続流動培養 / 連続流動培養法

Outline of Final Research Achievements

The aim of the present study was to determine the impact of H. pylori infection to gastrointestinal microbiota.　Several H. pylori strains isolated from family members were used to compare infectivity in Mongolian gerbils and growth in continuous flow culture. Most of the colonies isolated from the stomachs of Mongolian gerbils were determined as the same molecular type of dominant strain in all of the four grouped animals and H. pylori K25 was observed as the dominant strain. In continuous flow culture, two strains coexisted without changing the ratio of each other. H. pylori reduced the ratio of the predominant bacteria in the stomach of the animal at the early infection stage, but the original microbiota was reestablished after long-term infection. The antagonism between H. pylori infection and microbiota was observed.

Academic Significance and Societal Importance of the Research Achievements

常在細菌叢の役割の解析は古くから検討されてきたテーマであるが、メタゲノム解析、トランスクリプトーム解析、メタボローム解析などの手法を組み合わせたオミクス解析によってさらに大きな発見が期待される。本研究はその一端として、メタゲノム解析から常在細菌叢と外来病原細菌の拮抗現象を示すことができた。
またHelicobacter pylori感染症の、家族内感染1例について動物実験モデルを使って検証することができ、今後の感染予防に役立つ成果の一つと考える。

Research Products

• [Journal Article] Enhanced infectivity of strains of Helicobacter pylori isolated from children compared with parental strains (2019)
  • Author(s): Zaman Cynthia、Osaki Takako、Furuta Yoshikazu、Hojo Fuhito、Yonezawa Hideo、Konno Mutsuko、Kurata Satoshi、Hanawa Tomoko、Kamiya Shigeru
  • Journal Title: Journal of Medical Microbiology Volume: 68 Issue: 4 Pages: 633-641
  • DOI: 10.1099/jmm.0.000918
  • Peer Reviewed / Open Access
• [Journal Article] Influence of Intestinal Indigenous Microbiota on Intrafamilial Infection by Helicobacter pylori in Japan. (2018)
  • Author(s): Osaki T, Zaman C, Yonezawa H, Lin Y, Okuda M, Nozaki E, Hojo F, Kurata S, Hanawa T, Kikuchi S, Kamiya S.
  • Journal Title: Front Immunol. Volume: 9 Pages: 287-287
  • DOI: 10.3389/fimmu.2018.00287
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Usefulness of detection of clarithromycin-resistant Helicobacter pylori from fecal specimens for young adults treated with eradication therapy (2017)
  • Author(s): Osaki Takako、Mabe Katsuhiro、Zaman Cynthia、Yonezawa Hideo、Okuda Masumi、Amagai Kenji、Fujieda Shinji、Goto Mitsuhide、Shibata Wataru、Kato Mototsugu、Kamiya Shigeru
  • Journal Title: Helicobacter Volume: 22 Issue: 5
  • DOI: 10.1111/hel.12396
  • Peer Reviewed
• [Journal Article] Walker occupancy has an impact on changing airborne bacterial communities in an underground pedestrian space, as small-dust particles increased with raising both temperature and humidity (2017)
  • Author(s): Okubo Torahiko、Osaki Takako、Nozaki Eriko、Uemura Akira、Sakai Kouhei、Matushita Mizue、Matsuo Junji、Nakamura Shinji、Kamiya Shigeru、Yamaguchi Hiroyuki
  • Journal Title: PLOS ONE Volume: 12 Issue: 9 Pages: e0184980-e0184980
  • DOI: 10.1371/journal.pone.0184980
  • NAID: 120006347218
  • Peer Reviewed / Open Access
• [Journal Article] Helicobacter pylori sabA gene is associated with iron deficiency anemia in childhood and adolescence (2017)
  • Author(s): Kato Seiichi、Osaki Takako、Kamiya Shigeru、Zhang Xue-Song、Blaser Martin J.
  • Journal Title: PLOS ONE Volume: 12 Issue: 8 Pages: e0184046-e0184046
  • DOI: 10.1371/journal.pone.0184046
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diversification of the AlpB Outer Membrane Protein of Helicobacter pylori Affects Biofilm Formation and Cellular Adhesion (2017)
  • Author(s): Hideo Yonezawa, Takako Osaki, Toshiyuki Fukutomi, Tomoko Hanawa, Satoshi Kurat, Cynthia Zaman, Fuhito Hojo, Shigeru Kamiya
  • Journal Title: Journal of Bacteriology Volume: 199 Issue: 6 Pages: 199-199
  • DOI: 10.1128/jb.00729-16
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Usefulness of detection of clarithromycin-resistant Helicobacter pylori from fecal specimens for young adults treated with eradication therapy (2017)
  • Author(s): Osaki T, Mabe K, Zaman C, Yonezawa H, Okuda M, Amagai K, Fujieda S, Goto M, Shibata W, Kato M, Kamiya S.
  • Journal Title: Helicobacter Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microevolution of virulence-related genes in Helicobacter pylori familial infection. (2015)
  • Author(s): Furuta Y, Konno M, Osaki T, Yonezawa H, Ishige T, Imai Mi, Shiwa Y, Shibata-Hatta M, Kanesaki Y, Yoshikawa H, Kamiya S, Kobayashi I
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: e0127197-e0127197
  • DOI: 10.1371/journal.pone.0127197
  • Peer Reviewed / Open Access
• [Journal Article] Low Prevalence and Incidence of Helicobacter pylori Infection in Children: A Population-Based Study in Japan. (2015)
  • Author(s): Okuda M, Osaki T, Lin Y, Yonezawa H, Maekawa K, Kamiya S, Fukuda Y, Kikuchi S.
  • Journal Title: Helicobacter Volume: 20 Issue: 2 Pages: 133-138
  • DOI: 10.1111/hel.12184
  • Peer Reviewed / Open Access
• [Presentation] Intra-familial transmission of Helicobacter pylori in Japanese families-Influence of intestinal indigenous microbiota (2018)
  • Author(s): Takako Osaki, Cynthia Zaman, Hideo Yonezawa, Yingsong Lin, Masumi Okuda, Fuhito Hojo, Shogo Kikuchi, Shigeru Kamiya.
  • Organizer: The 15th Japan-Korea Joint Symposium on Helicobacter infection
  • Int'l Joint Research
• [Presentation] Helicobacter pylori 感染胃炎とマイクロバイオーム (2018)
  • Author(s): 大﨑敬子 神谷 茂
  • Organizer: 第51回日本無菌生物ノートバイオロジー学会学術集会
• [Presentation] Gastro intestinal microbiota of Mongolian gerbil infected with Helicobacter pylori. (2018)
  • Author(s): 大﨑敬子、北条 史、米澤英雄、高橋志達、岡 健太郎、花輪智子、蔵田訓、神谷 茂
  • Organizer: 第91回日本細菌学会総会
• [Presentation] Characterization of Helicobacter pylori strains in continuous flow culture system. (2017)
  • Author(s): 大﨑敬子、ザマンシンシア、北条 史、米澤英雄、蔵田 訓、花輪智子、神谷 茂
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-19
• [Presentation] 16S metagenomic analysis for gastric microbiota of Mongolian gerbil infected with Helicobacter pylori. (2017)
  • Author(s): Osaki T, Yonezawa H, Takahashi M, Nozaki E, Zaman C, Hojo F, Kamiya S
  • Organizer: XXXth International Workshop on Helicobacter & Microbiota in Inflammation & Cancer
  • Int'l Joint Research
• [Presentation] Metagenomic analysis for microbial ecology between Helicobacter pylori and gastric microbiota in the chronic gastritis patients. (2017)
  • Author(s): Kamiya S, Osaki T, Tokunaga K, Yonezawa H, Tanaka A, Zaman C, Hojo F, Takahashi S.
  • Organizer: The 14th Japan-Korea Joint Symposium on Helicobacter infection
  • Int'l Joint Research
• [Presentation] The impact of Helicobacer pylori infection on gastric microbiota. (2017)
  • Author(s): Osaki T, Tokunaga K, Yonezawa H, Tanaka A, Motomichi T, Oka K, Zaman C, Hojo F, Kurata S, Hanawa T, Taguchi H, Kamiya S.
  • Organizer: The Joint Congress of the 19th ISG and the 50th Congress of JAGG and the 39th Congress of the SOMED,
  • Int'l Joint Research
• [Presentation] Metagenomic analysis for microbial ecology between Helicobacter pylori and gastric microbiota in the patients with atrophic gastritis. (2016)
  • Author(s): Takako Osaki, Kengo Tokunaga, Hideo Yonezawa, Akifumi Tanaka, Eriko Nozaki, Cynthia Zaman, Fuhito Hojo, Shinichi Takahashi, Shigeru Kamiya
  • Organizer: European Helicobacter and Microbiota Study Group; EHMSG XXIXth International Workshop on Helicobacter and Microbiota in Inflammation and Cancer
  • Place of Presentation: ドイツ、マグデブルグ
  • Year and Date: 2016-09-15
  • Int'l Joint Research
• [Presentation] Helicobacter pylori家族内感染と腸内常在細菌叢 (2016)
  • Author(s): 大崎 敬子 神谷 茂
  • Organizer: 19回日本臨床腸内微生物学会
  • Place of Presentation: 三鷹
  • Year and Date: 2016-08-27
• [Presentation] Animal study on Helicobacter pylori infection using the strains isolated from one family members. (2016)
  • Author(s): Cynthia Zaman, Takako Osaki, Hideo Yonezawa, Fuhito Hojo, Shigeru Kamiya
  • Organizer: The 13th Korea-Japan Joint Symposium on Helicobacter infection
  • Place of Presentation: 別府
  • Year and Date: 2016-06-25
  • Int'l Joint Research
• [Presentation] Helicobacter pylori感染と胃内細菌叢 (2016)
  • Author(s): 大崎敬子、徳永健吾、田中昭文、ザマンシンシア、米澤英雄、北条 史、高橋信一、神谷 茂
  • Organizer: 第22回日本ヘリコバクター学会学術集会
  • Place of Presentation: 別府
  • Year and Date: 2016-06-24
• [Presentation] 若年者除菌治療のための糞便DNAを用いたHelicobacter pylori薬剤耐性遺伝子変異の検出と分離菌株の薬剤感受性 (2016)
  • Author(s): 大崎敬子、米澤英雄、蔵田 訓、神谷 茂
  • Organizer: 第89回日本感染症学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-16
• [Presentation] Helicobacter pylori の家族内感染の解析と分 離菌株のスナネズミ感染性の比較 (2016)
  • Author(s): 神谷 茂，Cynthia Zaman，米澤 英雄，大崎 敬子
  • Organizer: 第89回日本細菌学会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-23
• [Presentation] Metagenomic study on gastric microbiota of the patients with chronic gastritis. (2016)
  • Author(s): 大崎敬子、Cynthia Zaman、米澤英雄、高橋志達、岡健太郎、北条史、蔵田訓、花輪智子、神谷茂
  • Organizer: 第89回日本細菌学会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-23
• [Presentation] 16S metagenomic study on gastric microbiota of the patients with chronic gastritis. (2015)
  • Author(s): Osaki T, Tokunaga K, Yonezawa H, Tanaka A, Nozaki E, Zaman C, Hojo F, Takahashi S, Kamiya S.
  • Organizer: 18th International workshop on Canmpylobacter, Helicobacter andrelated organisms
  • Place of Presentation: Rotorua,ニュージーランド
  • Year and Date: 2015-11-01
  • Int'l Joint Research
• [Presentation] Dominantly persistent infection in gastric mucosa of Mongolian gerbils with H. pylori strain isolated from 3 children compared to those from their parents. (2015)
  • Author(s): Kamiya S, Zaman C, Yonezawa H, Hojo F, Osaki T
  • Organizer: 18th International workshop on Canmpylobacter, Helicobacter andrelated organisms
  • Place of Presentation: Rotorua,ニュージーランド
  • Year and Date: 2015-11-01
  • Int'l Joint Research
• [Presentation] 慢性胃炎患者における胃内常在細菌叢の メタゲノム解析 (2015)
  • Author(s): 大﨑敬子 、徳永健吾、米澤 英雄 、ザマン シンシア 、田中昭文、北 条 史、 花輪 智子、高橋信一、神谷 茂
  • Organizer: 第21回日本ヘリコバクター学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2015-06-26