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Trans-Omics approach to understand the pathogenesis of H. pylori infected and uninfected gastric cancer.

Research Project

Project/Area Number 21K08010
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionOita University

Principal Investigator

Matsumoto Takashi  大分大学, 医学部, 助教 (50609667)

Co-Investigator(Kenkyū-buntansha) 塚本 善之  大分大学, 医学部, 助教 (00433053)
山岡 吉生  大分大学, 医学部, 教授 (00544248)
赤田 純子  大分大学, 医学部, 助教 (30346548)
Project Period (FY) 2021-04-01 – 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsピロリ菌感染症 / 胃癌 / 次世代シーケンス / 胃オルガノイド / RNA-Seq / メタボロミクス / ピロリ菌未感染胃癌 / 16S rRNAメタゲノム解析 / オルガノイド
Outline of Research at the Start

ピロリ菌は、胃癌をはじめとする消化器疾患を引き起こす。しかし、実際には、ピロリ菌感染者の数%しか胃癌を発症せず、生涯を通じて殆ど症状が現れない不顕性感染例も多く存在する。また、本邦では、すべてのピロリ菌感染胃炎患者に対する除菌治療が保険収載となって以降、全国的な除菌治療が実施されているにも関わらず、未だに、胃癌は、本邦における部位別がん死亡率の上位である。即ち、ピロリ菌除菌=胃癌発生ゼロではなく、ピロリ菌感染以外にも発がんに関与する因子が存在することが伺える。そこで本研究では、トランスオミクス解析という新たなアプローチにより、胃癌発症機序およびピロリ菌未感染胃癌の解明に挑む。

Outline of Final Research Achievements

This study isolated and identified a novel bacterium involved in gastric cancer pathogenesis by a mechanism distinct from Helicobacter pylori (H. pylori). Using gastric organoids, which more closely mimic the in vivo environment, it was further shown that this bacterium induces DNA double-strand breaks, which trigger gastric cancer pathogenesis, via the induction of reactive oxygen species and also suppresses the DNA damage response pathway. It has also been suggested that the differences in the attachment mechanism due to the genotype of the outer membrane protein of H. pylori affect the mucosal environment of the stomach and influence the colonization and composition of other bacterial flora that may be involved in the pathogenesis of gastric and duodenal diseases.

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌は、胃癌や消化性潰瘍の原因微生物として広く認知され、現在、国内では積極的な内視鏡検査と除菌治療が進められている。一方で、ピロリ菌未感染胃癌や除菌後胃癌など、これまで注目されてこなかった病態の存在が浮き彫りになり、科学的な検証が必要である。本研究では、ピロリ菌以外の病原微生物の存在やその病原性を明らかにし、ピロリ菌が胃内のその他細菌叢の構成をどのように制御しているのかを実験的に示すことができた。今後、関連する胃・十二指腸疾患の臨床疫学データの蓄積が進み、予防策の立案に繋げるなど社会還元を期待する。

Report

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

    (48 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (14 results) Journal Article (16 results) (of which Int'l Joint Research: 15 results,  Peer Reviewed: 16 results,  Open Access: 16 results) Presentation (11 results) (of which Int'l Joint Research: 11 results,  Invited: 2 results) Remarks (7 results)

  • [Int'l Joint Research] モンゴル医科学大学(モンゴル)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] アイルランガ大学/インドネシア大学(インドネシア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] アガカーン大学/ケニヤッタ大学(ケニア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 王立疾病管理センター/ケサルギャルポ王立医科大学/ジグミ・ドルジ・ワンチュク国立総合病院(ブータン)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 108病院(ベトナム)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Universitas Airlangga/University of Muhammadiyah Surabaya(インドネシア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] MNUMS(モンゴル)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Royal Centre for Disease Control/KGUMSB/JDWNRH(ブータン)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Mbuji Mayi(コンゴ民主共和国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Institut Pasteur of Shanghai(中国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Cho Ray Hospital, Ho Chi Minh/108 Central Hospital, Hanoi(ベトナム)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] MNUMS(モンゴル)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy2024

    • Author(s)
      Fuchino Takafumi、Kurogi Shusaku、Tsukamoto Yoshiyuki、Shibata Tomotaka、Fumoto Shoichi、Fujishima Hajime、Kinoshita Keisuke、Mizukami Kazuhiro、Kodama Masaaki、Inomata Masafumi、Murakami Kazunari、Moriyama Masatsugu、Hijiya Naoki
    • Journal Title

      Human Cell

      Volume: 37 Issue: 2 Pages: 491-501

    • DOI

      10.1007/s13577-023-01020-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Study of Helicobacter pylori Isolated from a High-Gastric-Cancer-Risk Population: Unveiling the Comprehensive Analysis of Virulence-Associated Genes including Secretion Systems, and Genome-Wide Association Study2023

    • Author(s)
      Saruuljavkhlan B, Alfaray RI, Oyuntsetseg K, Gantuya B, Khangai A, Renchinsengee N, Matsumoto T, Akada J, Azzaya D, Davaadorj D, Yamaoka Y.
    • Journal Title

      Cancers (Basel)

      Volume: 15 Issue: 18 Pages: 4528-4528

    • DOI

      10.3390/cancers15184528

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh.2023

    • Author(s)
      Fauzia, Kartika Afrida, Hafeza Aftab, Evariste Tshibangu-Kabamba, Ricky Indra Alfaray, Batsaikhan Saruuljavkhlan, Alain Cimuanga-Mukanya, Takashi Matsumoto, Phawinee Subsomwong, Junko Akada, Muhammad Miftahussurur, and Yoshio Yamaoka.
    • Journal Title

      Antibiotics

      Volume: 12 Issue: 2 Pages: 279-279

    • DOI

      10.3390/antibiotics12020279

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exploring Alternative Treatment Choices for Multidrug-Resistant Clinical Strains of Helicobacter pylori in Mongolia2023

    • Author(s)
      Khangai Ayush、Saruuljavkhlan Batsaikhan、Azzaya Dashdorj、Gantuya Boldbaatar、Oyuntsetseg Khasag、Akada Junko、Matsumoto Takashi、Yamaoka Yoshio
    • Journal Title

      Microorganisms

      Volume: 11 Issue: 12 Pages: 2852-2852

    • DOI

      10.3390/microorganisms11122852

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Utilization of an Automated Latex Agglutination Turbidity Assay for Assessing Gastric Mucosal Alteration during Helicobacter pylori Infection2023

    • Author(s)
      Khangai Ayush、Akada Junko、Saruuljavkhlan Batsaikhan、Gantuya Boldbaatar、Azzaya Dashdorj、Oyuntsetseg Khasag、Davaadorj Duger、Uchida Tomohisa、Matsumoto Takashi、Yamaoka Yoshio
    • Journal Title

      Gut and Liver

      Volume: 18 Issue: 1 Pages: 60-69

    • DOI

      10.5009/gnl220464

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Global Antimicrobial Resistance Gene Study of Helicobacter pylori: Comparison of Detection Tools, ARG and Efflux Pump Gene Analysis, Worldwide Epidemiological Distribution, and Information Related to the Antimicrobial-Resistant Phenotype2023

    • Author(s)
      Alfaray Ricky Indra、Saruuljavkhlan Batsaikhan、Fauzia Kartika Afrida、Torres Roberto C.、Thorell Kaisa、Dewi Selva Rosyta、Kryukov Kirill A.、Matsumoto Takashi、Akada Junko、Vilaichone Ratha-korn、Miftahussurur Muhammad、Yamaoka Yoshio
    • Journal Title

      Antibiotics

      Volume: 12 Issue: 7 Pages: 1118-1118

    • DOI

      10.3390/antibiotics12071118

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic determinants of Biofilm formation of Helicobacter pylori using whole-genome sequencing2023

    • Author(s)
      Fauzia Kartika Afrida、Aftab Hafeza、Miftahussurur Muhammad、Waskito Langgeng Agung、Tuan Vo Phuoc、Alfaray Ricky Indra、Matsumoto Takashi、Yurugi Michiyuki、Subsomwong Phawinee、Kabamba Evariste Tshibangu、Akada Junko、Yamaoka Yoshio
    • Journal Title

      BMC Microbiology

      Volume: 23 Issue: 1 Pages: 159-159

    • DOI

      10.1186/s12866-023-02889-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative genomics of two Vietnamese Helicobacter pylori strains, CHC155 from a non-cardia gastric cancer patient and VN1291 from a duodenal ulcer patient.2023

    • Author(s)
      Phuc BH, Tuan VP, Binh TT, Tung PH, Tri TD, Dung HDQ, Thuan NPM, Fauzia KA, Tshibangu-Kabamba E, Alfaray RI, Saruuljavkhlan B, Matsumoto T, Akada J, Yamaoka Y.
    • Journal Title

      Sci Rep

      Volume: 13 Issue: 1 Pages: 8869-8869

    • DOI

      10.1038/s41598-023-35527-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficient Establishment of Bile-Derived Organoids From Patients With Biliary Cancer.2023

    • Author(s)
      Kinoshita K, Tsukamoto Y, Hirashita Y, Fuchino T, Kurogi S, Uchida T, Nakada C, Matsumoto T, Okamoto K, Motomura M, Fukuchi S, Sagami R, Nagai T, Gotoh Y, Fukuda K, Ogawa R, Mizukami K, Okimoto T, Kodama M, Murakami K, Moriyama M, Hijiya N.
    • Journal Title

      Lab Invest.

      Volume: 103 Issue: 6 Pages: 100105-100105

    • DOI

      10.1016/j.labinv.2023.100105

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low-grade intestinal metaplasia in Indonesia: Insights into the expression of proinflammatory cytokines during Helicobacter pylori infection and unique East-Asian CagA characteristics2023

    • Author(s)
      Miftahussurur Muhammad、Alfaray Ricky Indra、Fauzia Kartika Afrida、Dewayani Astri、Doohan Dalla、Waskito Langgeng Agung、Rezkitha Yudith Annisa Ayu、Utomo Didik Huswo、Somayana Gde、Fahrial Syam Ari、Lubis Masrul、Akada Junko、Matsumoto Takashi、Yamaoka Yoshio
    • Journal Title

      Cytokine

      Volume: 163 Pages: 156122-156122

    • DOI

      10.1016/j.cyto.2022.156122

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of gastric microbiota and Helicobacter pylori infection in gastroesophageal reflux disease2022

    • Author(s)
      Sugihartono Titong、Fauzia Kartika Afrida、Miftahussurur Muhammad、Waskito Langgeng Agung、Rejeki Purwo Sri、I’tishom Reny、Alfaray Ricky Indra、Doohan Dalla、Amalia Rizki、Savitri Camilia Metadea Aji、Rezkitha Yudith Annisa Ayu、Akada Junko、Matsumoto Takashi、Yamaoka Yoshio
    • Journal Title

      Gut Pathogens

      Volume: 14 Issue: 1 Pages: 38-38

    • DOI

      10.1186/s13099-022-00510-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Helicobacter pylori genomes reveal Paleolithic human migration to the east end of Asia2022

    • Author(s)
      Suzuki Rumiko、Saitou Naruya、Matsuari Osamu、Shiota Seiji、Matsumoto Takashi、Akada Junko、Kinjo Nagisa、Kinjo Fukunori、Teruya Kuniko、Shimoji Makiko、Shiroma Akino、Kato Mototsugu、Satou Kazuhito、Hirano Takashi、Asaka Masahiro、Kryukov Kirill、Moodley Yoshan、Yamaoka Yoshio
    • Journal Title

      iScience

      Volume: 25 Issue: 7 Pages: 104477-104477

    • DOI

      10.1016/j.isci.2022.104477

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Seroepidemiological survey of the prevalence of Helicobacter pylori infection in Sabah, Malaysia2022

    • Author(s)
      Mori Daisuke、John Jecelyn Leaslie、Sabri Shahnaz Irwani Binti、Shaharom Saliz Mazrina Binti、Iha Hidekatsu、Yamaoka Yoshio、Matsumoto Takashi、Ahmed Kamruddin
    • Journal Title

      IJID Regions

      Volume: 2 Pages: 126-129

    • DOI

      10.1016/j.ijregi.2021.12.012

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Next-Generation Sequencing-Based Study of Helicobacter pylori Isolates from Myanmar and Their Susceptibility to Antibiotics2022

    • Author(s)
      Subsomwong Phawinee、Doohan Dalla、Fauzia Kartika Afrida、Akada Junko、Matsumoto Takashi、Yee Than Than、Htet Kyaw、Waskito Langgeng Agung、Tuan Vo Phuoc、Uchida Tomohisa、Matsuhisa Takeshi、Yamaoka Yoshio
    • Journal Title

      Microorganisms

      Volume: 10 Issue: 1 Pages: 196-196

    • DOI

      10.3390/microorganisms10010196

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates2021

    • Author(s)
      Tuan V P、Yahara K、Dung H D Q、Binh T T、Huu T P、Tri T D、Thuan N P M、Khien V V、Trang T T H、Phuc B H、Tshibangu-Kabamba E、Matsumoto T、Akada J、Suzuki R、Okimoto T、Kodama M、Murakami K、Yano H、Fukuyo M、Takahashi N、Kato M、Nishiumi S、Azuma T、Ogura Y、Hayashi T、Toyoda A、Kobayashi I、Yamaoka Y
    • Journal Title

      Microbial Genomics

      Volume: 7 Issue: 11 Pages: 1-17

    • DOI

      10.1099/mgen.0.000680

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of the diagnostic accuracy and relevance of a novel ELISA system developed for seroepidemiologic surveys of Helicobacter pylori infection in African settings2021

    • Author(s)
      Tshibangu-Kabamba Evariste、Phuc Bui Hoang、Tuan Vo Phuoc、Kayiba Nadine Kalenda、Rosas-Aguirre Angel、Devleesschauwer Brecht、Cimuanga-Mukanya Alain、Ngoma Kisoko Patrick de Jsus、Disashi Ghislain Tumba、Mumba Ngoyi Dieudonn、Kido Yasutoshi、Speybroeck Niko、Yamaoka Yoshio
    • Journal Title

      PLOS Neglected Tropical Diseases

      Volume: 15 Issue: 9 Pages: e0009763-e0009763

    • DOI

      10.1371/journal.pntd.0009763

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Entroccus Hirae Attenuates chemokine and Induces Dna Damage In Gastric Epithelial Cell2023

    • Author(s)
      Saruuljavkhlan B, Matsumoto T, Yamaoka Y.
    • Organizer
      Digestive Disease Week 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh.2023

    • Author(s)
      Fauzia, Kartika Afrida, Hafeza Aftab, Evariste Tshibangu-Kabamba, Ricky Indra Alfaray, Batsaikhan Saruuljavkhlan, Alain Cimuanga-Mukanya, Takashi Matsumoto, Phawinee Subsomwong, Junko Akada, Muhammad Miftahussurur, and Yoshio Yamaoka
    • Organizer
      International Symposium on Helicobacter and Upper Gastrointestinal Disease
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Outer membrane protein HopF is involved in biofilm formation and virulence in Helicobacter pylori.2023

    • Author(s)
      Kartika Afrida Fauzia, Yuri Sugawara, Mayu Obata, Rizki Amalia, Ricky Indra Alfaray, Camilia Metadea, Junko Akada, Takashi Matsumoto, Muhammad Miftahussurur, Yoshio Yamaoka
    • Organizer
      The 19th Korea-Japan H. pylori Joint Symposium, Gut and liver
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Biofilm Formation and antibiotic resistance phenotype of Helicobacter pylori clinical isolates.2022

    • Author(s)
      Fauzia KA, Matsumoto T, Akada J, Yonezawa H, Kamiya S, Yamaoka Y.
    • Organizer
      The 18th Japan-Korea H. pylori Joint Symposium.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] The impact of mobile genetic elemants and toxin-antitoxin system on Helicobacter pylori adaptability and antimicrobial resistance: A wisdom from Japan-South Korea whole-genome sequence collection.2022

    • Author(s)
      Alfaray RI, Batsaikhan S, Fauzia KA, Akada J, Matsumoto T, Yamaoka Y
    • Organizer
      The 18th Japan-Korea H. pylori Joint Symposium.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of the Helicobacter pylori genomic islands in a high gastric cancer region.2022

    • Author(s)
      Batsaikhan S, Alfaray RI, Matsumoto T, Akada J, Yamaoka Y.
    • Organizer
      The 18th Japan-Korea H. pylori Joint Symposium.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Global genome study of helicobacter pylori phage opens new paradigm on their worldwide distribution, genetic feature, and impacts on antimicrobial resistance, disease advancement, and achievement for phage-based therapy2022

    • Author(s)
      Alfaray IR, Saruuljavkhlan B, Fauzia KA, Matsumoto T, Yamaoka Y.
    • Organizer
      International Digestive Disease Forum
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel pathogen enterococcus hirae induced dysbiosis in the stomach and the genomic instability to promote gastric cancer.2022

    • Author(s)
      Saruuljavkhlan B, Gantuya B, Akada J, Matsumoto T, Alfaray RI, Oyuntsetseg K, Yamaoka Y.
    • Organizer
      International Digestive Disease Forum
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Next Generation Sequencing Technique of H. pylori Infection and Gastric Microbiome2021

    • Author(s)
      Takashi Matsumoto
    • Organizer
      Univeristas Airlangga and Oita University 1st Joint symposium & workshop in Medicine.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] H. pylori Infection and Gastric Microbiome2021

    • Author(s)
      Takashi Matsumoto
    • Organizer
      Chulalongkorn University-Oita University Joint Mini-Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Introduction of gastric microbiome study: from basis to study example2021

    • Author(s)
      Takashi Matsumoto
    • Organizer
      Basic Research for Young Scientist (BAYONET)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 大分大学医学部環境・予防医学講座

    • URL

      https://oitadepm.com/

    • Related Report
      2023 Annual Research Report
  • [Remarks] ピロリ菌感染症関連死撲滅に向けた中核拠点形成事業

    • URL

      https://satreps-oitauniv.com/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 大分大学医学部環境予防医学講座

    • URL

      https://oitadepm.com/

    • Related Report
      2022 Research-status Report
  • [Remarks] Researchmap

    • URL

      https://researchmap.jp/-oita-u%5Ematsumoto

    • Related Report
      2022 Research-status Report 2021 Research-status Report
  • [Remarks] SATREPS

    • URL

      https://satreps-oitauniv.com/

    • Related Report
      2022 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      https://oitadepm.com/

    • Related Report
      2021 Research-status Report
  • [Remarks] 日本の研究.com

    • URL

      https://research-er.jp/researchers/view/589799

    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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