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Preventive effects of lifestyle-related diseases by improving dysbiosis

Research Project

Project/Area Number 20K08194
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionJuntendo University

Principal Investigator

Shimizu Toshiaki  順天堂大学, 医学部, 特任教授 (30260889)

Co-Investigator(Kenkyū-buntansha) 東海林 宏道  順天堂大学, 大学院医学研究科, 教授 (30365621)
大塚 宜一  順天堂大学, 医学部, 客員教授 (90338335)
Project Period (FY) 2020-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords生活習慣病 / Dysbiosis / DOHaD説 / 低出生体重児 / 腸内細菌 / dysbiosis / プロバイオティクス
Outline of Research at the Start

低出生体重児では、将来生活習慣病に罹患しやすいことが知られている(DOHaD説)。一方、腸内細菌叢の乱れ(dysbiosis)が新生児・乳児の未熟な腸管機能に悪影響を及ぼし、小児期のみならず成人となった後にも肥満や生活習慣病をはじめとする様々な問題を引き起こす可能性が考えられているが、そのメカニズムについての十分な検討は行われていない。
そこで本研究では、培養細胞実験および動物実験を行い、dysbiosisと将来の生活習慣病の発症との関係を明らかにし、DOHaD説で説明される生活習慣病の発症予防のための有効な介入方法について検証を行っていく。

Outline of Final Research Achievements

The purpose of this study was to clarify the relationship between postnatal dysbiosis and future lifestyle-related diseases, and to elucidate the mechanism of lifestyle-related diseases in low-birth-weight infants as explained by the DOHaD theory.
Pregnant rats were divided into two groups: one group was fed a low-protein diet from the first day of pregnancy until delivery, and the other group was fed a normal diet. From 3 to 12 weeks of age, the largest proportion of bacteria in the stools of both groups were Firmicutes, followed by Bacteroidetes, while at 2 weeks of age, Firmicutes were predominant in the low-protein diet group, followed by Proteobacteria. Although there were differences in β-diversity between the two groups, there was a similar tendency for the flora to become more stable with age. It is possible that early postnatal dysbiosis may be involved in the development of lifestyle-related diseases in low-birth-weight infants.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、DOHaD説である低出生体重児における生活習慣病の発症に生後早期のdysbiosisが関与している可能性が明らかとなり、低出生体重児に対する生後早期の栄養法の改善やプロバイオティクスの投与などが将来の生活習慣病の発症を予防できれば、学術的意義は高いものと考える。さらに、妊娠中の低栄養が低出生体重児の出産や児の将来の生活習慣病の発症に関係することが明らかとなれば、妊娠中の栄養管理の重要性の啓発となり、社会的意義は高いと考える。

Report

(6 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (42 results)

All 2024 2023 2022 2021 2020 2018 Other

All Journal Article (25 results) (of which Peer Reviewed: 23 results,  Open Access: 20 results) Presentation (16 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Journal Article] Infant Formula with 50% or More of Palmitic Acid Bound to the sn-2 Position of Triacylglycerols Eliminate the Association between Formula-Feeding and the Increase of Fecal Palmitic Acid Levels in Newborns: An Exploratory Study2024

    • Author(s)
      Shoji Hiromichi、Arai Hiroko、Kakiuchi Satsuki、Ito Atsushi、Sato Keigo、Jinno Shinji、Takahashi Naoto、Masumoto Kenichi、Yoda Hitoshi、Shimizu Toshiaki
    • Journal Title

      Nutrients

      Volume: 16 Issue: 11 Pages: 1558-1558

    • DOI

      10.3390/nu16111558

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Propionimicrobium lymphophilum in urine of children with monosymptomatic nocturnal enuresis2024

    • Author(s)
      Nishizaki Naoto、Oshiro Satoshi、Tohya Mari、Watanabe Shin、Okazaki Tadaharu、Takahashi Ken、Kirikae Teruo、Shimizu Toshiaki
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 14 Pages: 1377992-1377992

    • DOI

      10.3389/fcimb.2024.1377992

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The impact of cyclooxygenase inhibitor use on urinary prostaglandin metabolites in preterm infants2024

    • Author(s)
      Ohkawa Natsuki、Shoji Hiromichi、Ikeda Naho、Murano Yayoi、Okuno Toshiaki、Kantake Masato、Yokomizo Takehiko、Shimizu Toshiaki
    • Journal Title

      Pediatrics and Neonatology

      Volume: 65 Issue: 2 Pages: 123-126

    • DOI

      10.1016/j.pedneo.2023.08.002

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Body Mass Index Changes at 1.5 and 3 Years of Age Affect Adult Body Composition2024

    • Author(s)
      Miyayama Chiharu、Shoji Hiromichi、Murano Yayoi、Ito Kanami、Saita Mizue、Naito Toshio、Fukuda Hiroshi、Shimizu Toshiaki
    • Journal Title

      Pediatric Reports

      Volume: 16 Issue: 3 Pages: 669-677

    • DOI

      10.3390/pediatric16030056

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iron and zinc deficiency affect adolescent school girls' behavior.2024

    • Author(s)
      Yoshida N, Kawato C, Niijima S, Ohtomo Y, Shimizu T.
    • Journal Title

      Biological Trace Element Research.

      Volume: 34 Pages: 11-19

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal Protein Restriction Inhibits Insulin Signaling and Insulin Resistance in the Skeletal Muscle of Young Adult Rats2024

    • Author(s)
      AWATA KENTARO、SHOJI HIROMICHI、ARAI YOSHITERU、SANTOSA IRENA、TOKITA KAZUHIDE、MURANO YAYOI、SHIMIZU TOSHIAKI
    • Journal Title

      Juntendo Medical Journal

      Volume: 70 Issue: 2 Pages: 142-151

    • DOI

      10.14789/jmj.JMJ23-0029-OA

    • ISSN
      2187-9737, 2188-2126
    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immaturity of gut functions and induction of tolerance during early infancy2024

    • Author(s)
      Ohtsuka Yoshikazu、Shimizu Toshiaki
    • Journal Title

      Pediatrics International

      Volume: 67 Issue: 1

    • DOI

      10.1111/ped.15855

    • Related Report
      2024 Annual Research Report
  • [Journal Article] 特集 小児の疾患と腸内細菌叢との関係を探る 特集にあたって.2024

    • Author(s)
      清水俊明
    • Journal Title

      Microbiome Science

      Volume: 3 Pages: 71-71

    • Related Report
      2024 Annual Research Report
  • [Journal Article] Effects of fetal growth restriction on postnatal gut microbiota in a rat model2023

    • Author(s)
      Arai Yoshiteru、Shoji Hiromichi、Santosa Irena、Awata Kentaro、Tokita Kazuhide、Shimizu Toshiaki
    • Journal Title

      Journal of Pediatric Gastroenterology & Nutrition

      Volume: Publish Ahead of Print Issue: 2

    • DOI

      10.1097/mpg.0000000000003805

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between caesarean delivery and weight status in early childhood: a birth cohort study in Japan2023

    • Author(s)
      Miyayama Chiharu、Morisaki Naho、Ogawa Kohei、Tanaka Hisako、Shoji Hiromichi、Shimizu Toshiaki、Sago Haruhiko、Horikawa Reiko、Urayama Kevin
    • Journal Title

      Sci Rep

      Volume: 13 Pages: 19612-19612

    • DOI

      10.21203/rs.3.rs-3087650/v1

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic and Skeletal Muscle Autophagy Marker Levels in Rat Models of Prenatal and Postnatal Protein Restriction2023

    • Author(s)
      Santosa Irena、Shoji Hiromichi、Arai Yoshiteru、Awata Kentaro、Tokita Kazuhide、Shimizu Toshiaki
    • Journal Title

      Nutrients

      Volume: 15 Issue: 13 Pages: 3058-3058

    • DOI

      10.3390/nu15133058

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Skeletal Muscle Insulin Resistance in a Novel Fetal Growth Restriction Model2023

    • Author(s)
      Tokita Kazuhide、Shoji Hiromichi、Arai Yoshiteru、Awata Kentaro、Santosa Irena、Murano Yayoi、Shimizu Toshiaki
    • Journal Title

      Pediatric Reports

      Volume: 15 Issue: 1 Pages: 45-54

    • DOI

      10.3390/pediatric15010006

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mammals sustain amino acid homochirality against chiral conversion by symbiotic microbes2023

    • Author(s)
      Gonda Yusuke、Matsuda Akina、Adachi Kenichiro、Ishii Chiharu、Suzuki Masataka、Osaki Akina、Mita Masashi、Nishizaki Naoto、Ohtomo Yoshiyuki、Shimizu Toshiaki、Yasui Masato、Hamase Kenji、Sasabe Jumpei
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 15 Pages: 1402-1409

    • DOI

      10.1073/pnas.2300817120

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations between size at birth and size at 6?years among preterm infants: a retrospective cohort study2022

    • Author(s)
      Awata Kentaro、Shoji Hiromichi、Santosa Irena、Ikeda Naho、Murano Yayoi、Ohkawa Natsuki、Nishizaki Naoto、Hisata Ken、Kantake Masato、Obinata Kaoru、Shimizu Toshiaki
    • Journal Title

      Pediatrics International

      Volume: 64 Issue: 1 Pages: 14844-14844

    • DOI

      10.1111/ped.14844

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics and antimicrobial choice of pediatric bacterial enteritis in the Kanto region of Japan: A multicenter retrospective observational study2022

    • Author(s)
      Kasai Yuriha、Komatsu Mitsutaka、Toyama Yudai、Nakano Saki、Hisata Ken、Niizuma Takahiro、Obinata Kaoru、Shimizu Toshiaki
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 28 Issue: 6 Pages: 723-728

    • DOI

      10.1016/j.jiac.2021.08.022

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Growth Trajectories during the First 6 Years in Survivors Born at Less Than 25 Weeks of Gestation Compared with Those between 25 and 29 Weeks2022

    • Author(s)
      Shoji Hiromichi、Murano Yayoi、Nojiri Shuko、Arai Yoshiteru、Awata Kentaro、Ikeda Naho、Ohkawa Natsuki、Nishizaki Naoto、Suganuma Hiroki、Hisata Ken、Kantake Masato、Obinata Kaoru、Shimizu Toshiaki
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 5 Pages: 1418-1418

    • DOI

      10.3390/jcm11051418

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular epidemiology of meticillin-susceptible Staphylococcus aureus in the neonatal intensive care unit2022

    • Author(s)
      Toyama Y.、Hisata K.、Kasai Y.、Nakano S.、Komatsu M.、Shimizu T.
    • Journal Title

      Journal of Hospital Infection

      Volume: 129 Pages: 75-81

    • DOI

      10.1016/j.jhin.2022.07.026

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 莢膜血清型23B型肺炎球菌による細菌性髄膜炎を発症した小児例 血清型およびMLST解析の検討.2021

    • Author(s)
      宮崎萌香,馬場洋介,寒竹正人,清水俊明.
    • Journal Title

      アレルギーの臨床

      Volume: 41 Pages: 427-431

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 母子間の水平伝播が示唆されたStreptococcus gallolyticus subsp.pasteurianusによる細菌性髄膜炎.2021

    • Author(s)
      神山恵里佳,笠井悠里葉,幾瀬圭,岩崎友弘,久田研,清水俊明.
    • Journal Title

      小児感染免疫

      Volume: 33 Pages: 127-132

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Colonization of Supplemented Bifidobacterium breve M-16V in Low Birth Weight Infants and Its Effects on Their Gut Microbiota Weeks Post-administration2020

    • Author(s)
      Horigome A, Hisata K, Odamaki T, Iwabuchi N, Xiao JZ, Shimizu T.
    • Journal Title

      Front Microbiol

      Volume: 12 Pages: 610080-610080

    • DOI

      10.3389/fmicb.2021.610080

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IGF1 gene is epigenetically activated in preterm infants with intrauterine growth restriction2020

    • Author(s)
      Kantake M, Ikeda N, Nakaoka H, Ohkawa N, Tanaka T, Miyabayashi K, Shoji H, Shimizu T.
    • Journal Title

      Clinical Epigenetics

      Volume: 12 Issue: 1 Pages: 108-108

    • DOI

      10.1186/s13148-020-00901-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Policy Statement of Enteral Nutrition for Preterm and Very Low Birthweight Infants.2020

    • Author(s)
      Mizuno K, Shimizu T, Shinobu Ida, Ito S, Inokuchi M, Ohura T,Okumura A, KawaiM,Kikuchi T, Sakurai M, Sugihara S, Suzuki M,Takitani K,Tanaka D,Mushiake S,Yoshiike N,Kodama H,Kazuo Okada K, Tsutsumi C, Hara M, Hanawa Y,Kawakami K, Inomata H, Oguni T,Bito Y,Uchida K, Akihide Sugiyama A.
    • Journal Title

      Pediatr Int.

      Volume: 62 Issue: 2 Pages: 124-127

    • DOI

      10.1111/ped.14067

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intrauterine growth restriction affects z-scores of anthropometric parameters during the first 6 years in very low-birth-weight-children born at less than 30 weeks of gestation.2020

    • Author(s)
      Shoji H, Watanabe A, Awaji A, Ikeda N, Hosozawa M, Ohkawa N, Nishizaki N, Hisata K, Kantake M, Obinata K, Shimizu T.
    • Journal Title

      J Dev Orig Health Dis

      Volume: 11 Issue: 1 Pages: 44-48

    • DOI

      10.1017/s2040174419000369

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidemiology of methicillin-resistant Staphylococcus aureus in a Japanese neonatal intensive care unit2020

    • Author(s)
      Tsujiwaki A, Hisata K, Tohyama Y, Matsunaga N, Uehara Y, Sasaki T, Hiramatsu K, Shimizu T.
    • Journal Title

      Pediatr Int

      Volume: 62 Issue: 8 Pages: 811-919

    • DOI

      10.1111/ped.14241

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Choline-related metabolites influenced by feeding patterns in preterm and term infants2018

    • Author(s)
      Shoji Hiromichi、Taka Hikari、Kaga Naoko、Ikeda Naho、Hisata Ken、Miura Yoshiki、Shimizu Toshiaki
    • Journal Title

      The Journal of Maternal-Fetal & Neonatal Medicine

      Volume: ー Issue: 2 Pages: 1-6

    • DOI

      10.1080/14767058.2018.1488165

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Antigen-Specific IgA and Secretory IgA Play Key Roles in Mucosal Immune Responses in Food-Allergic Children.2024

    • Author(s)
      Baba Y, Takaoka Y, Kudo T, Ohtsuka Y, Shimizu T.
    • Organizer
      European Association of Allergy & Immunology Congress 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 母子手帳情報を活用した乳幼児期の育児困難感の経過パターンとその関連因子の検討.2024

    • Author(s)
      及川奈央, 細澤麻里子, 井神健太, 小川悠, 中村明雄, 三友聡美, 岩崎友弘, 清水俊明.
    • Organizer
      第127回日本小児科学会学術集会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 生後1か月の早産児・正期産児における尿中アンジオテンシノーゲンおよびACE2排泄についての検討.2024

    • Author(s)
      荒井美輝, 東海林宏道, Irena Santosa, 粟田健太郎, 大川夏紀, 菅沼広樹, 清水俊明.
    • Organizer
      第60回日本周産期・新生児医学会学術集会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 当院におけるearly term児の予後.2024

    • Author(s)
      田畑恭輔, 村野弥生, 中澤友幸, 北村翼, 坂巻健, 米岡大輔, 東海林宏道, 清水俊明.
    • Organizer
      第60回日本周産期・新生児医学会学術集会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 胎児発育不全が幼児期のメンタルヘルスに及ぼす影響についての検討.2024

    • Author(s)
      佐藤俊介, 東海林宏道, 村野弥生, 荒井美輝, 菅沼広樹, 清水俊明.
    • Organizer
      第127回日本小児科学会学術集会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 乳幼児期の BMI が成人期の体格に及ぼす影響についての検討.2023

    • Author(s)
      宮山千春,東海林宏道,村野弥生,清水俊明
    • Organizer
      第6回臨床DOHaDセミナー
    • Related Report
      2023 Research-status Report
  • [Presentation] 本邦における低出生体重児の年次推移についての検討.2023

    • Author(s)
      村野弥生,米岡大輔,坂巻健, 東海林宏道,Stuart Gilmour,清水俊明.
    • Organizer
      第126回日本小児科学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] 本邦における出生数および低出生体重児とHoliday effectの関係について.2023

    • Author(s)
      村野弥生,米岡大輔,東海林宏道,清水俊明.
    • Organizer
      第11回DOHaD学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] Low DNA methylation of IGF-I gene P2 promoter at birth in IUGR infants.2021

    • Author(s)
      Ikeda N, Kantake M, Ohkawa N, Shoji H, Shimizu T.
    • Organizer
      2021 Perinatal Society of Australia & New Zealand
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 蛋白制限による胎児発育不全モデルを用いた骨格筋インスリン抵抗性についての検討.2021

    • Author(s)
      粟田健太郎,荒井美輝, Irena Santosa,時田万英,東海林宏道,清水俊明.
    • Organizer
      第48回日本小児栄養消化器肝臓学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 在胎30週未満児における在胎週数と胎児発育が6歳時の体格予後に及ぼす影響についての検討.2021

    • Author(s)
      粟田健太郎,東海林宏道,村野弥生,池田奈帆,大川夏紀,西崎直人,久田研,寒竹正人,大日方薫,清水俊明.
    • Organizer
      第124回日本小児科学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 在胎25週未満生存児における6歳までの身体発育についての検討.2021

    • Author(s)
      荒井美輝,東海林宏道,池田奈帆,大川夏紀,西崎直人,久田研,寒竹正人,大日方薫,清水俊明.
    • Organizer
      第65回日本新生児成育医学会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] The prophylactic antimicrobial therapy criteria for very-low-birth-weight infants promote appropriate antimicrobial therapy.2020

    • Author(s)
      Kasai Y, Hisata K, Toyama Y, Nakano S, Igarashi N, Matsunaga N, Okawa N, Nishizaki N, Komatsu M, Kantake M, Obinata K, Shimizu T.
    • Organizer
      Virtual meeting of The European Society for Paediatric Infectious Diseases.
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大腸菌性髄膜炎を反復した乳児例における腸内細菌叢の経時的検討.2020

    • Author(s)
      新妻隆広,大日方薫,清水俊明.
    • Organizer
      第47回日本小児栄養消化器肝臓学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 生後1ヵ月児における尿中レジスチン排泄に関する検討.2020

    • Author(s)
      粟田健太郎, 東海林宏道, 池田奈帆, 大川夏紀, 寒竹正人, 清水俊明.
    • Organizer
      第123回日本小児科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 関連3施設における極低出生体重児の遅発型敗血症の傾向.2020

    • Author(s)
      笠井悠里葉,久田研,遠山雄大,中野沙季,五十嵐成,大川夏紀,西﨑直人,小松充孝,寒竹正人,大日方薫,清水俊明.
    • Organizer
      第52回日本小児感染症学会総会・学術集会
    • Related Report
      2020 Research-status Report
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    • Related Report
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Published: 2020-04-28   Modified: 2026-01-16  

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