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Strategy for the improvement of intestinal mucosal barrier function in low birth weight infants.

Research Project

Project/Area Number 17K10192
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionJuntendo University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 東海林 宏道  順天堂大学, 医学(系)研究科(研究院), 准教授 (30365621)
大塚 宜一  順天堂大学, 医学部, 客員准教授 (90338335)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsバリア機能 / 腸管粘膜 / プロバイオティクス / 低出生体重児 / 脂肪酸 / 腸内細菌 / 栄養学 / 感染症 / 微生物 / 免疫学 / 臨床
Outline of Final Research Achievements

We examined the effect of nutritional support and probiotics on the function of intestinal mucosal barrier function in low birth weight infants.
The influence of probiotics, including Bifidobacterium longum, Bifidobacterium breve, and Lactobacillus reuteri, on tight-junction function using T84 culture cells. The cells were studied at confluent, pre-confluent, and growing conditions. The mRNA expression of tight-junction proteins, such as TJP1, CLDN1, OCLN, and CLDN3 was evaluated.
The mRNA expression of TJP1, CLDN1, and OCLN of pre-confluent and growing conditions was significantly lower than that at confluent condition. After addition of Bifidobacterium CM the expression of TJP1, CLDN1, and OCLN was increased, and especially CLDN3. Moreover, the TJP1 expression was dose-dependently increased.

Academic Significance and Societal Importance of the Research Achievements

母乳栄養が低出生体重児の重症感染症やNECの予防に有効であることは臨床上経験されることであり、その機序として母乳成分による抗菌作用や免疫賦活作用、さらには腸内細菌叢に及ぼす影響などが知られている。本研究の結果を踏まえて、低出生体重児特に極低出生体重児に対する理想的な栄養法ならびにプロバイオティクス投与法を実行することで、順調な栄養摂取のみならず、致死的にもなり得る疾病の予防や後の合併症の予防にもつながると考える。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (34 results)

All 2020 2019 2018 2017 Other

All Journal Article (20 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Open Access: 14 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Book (1 results) Remarks (1 results)

  • [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 Annual Research 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 Annual Research 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 Annual Research Report 2019 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neonatal oral fluid as a transmission route for bifidobacteria to the infant gut immediately after birth.2019

    • Author(s)
      Toda K, Hisata K, Satoh T, Katsumata N, Odamaki T, Mitsuyama E, Katayama T, Kuhara T, Aisaka K, Shimizu T, Xiao JZ.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 8692-8692

    • DOI

      10.1038/s41598-019-45198-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of human breast milk on biological metabolism in infants.2019

    • Author(s)
      Shoji H, Shimizu T.
    • Journal Title

      Pediatr Int

      Volume: 61 Issue: 1 Pages: 6-15

    • DOI

      10.1111/ped.13693

    • Related Report
      2019 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Universal recommendations for the management of acute diarrhea in nonmalnourished children.2018

    • Author(s)
      Guarino A, Lo Vecchio A, Dias JA, Berkley JA, Boey C, Bruzzese D, Cohen MB, Cruchet S, Liguoro I, Salazar-Lindo E, Sandhu B, Sherman PM, Shimizu T.
    • Journal Title

      J Pediatr Gastroenterol Nutr

      Volume: 67 Issue: 5 Pages: 586-593

    • DOI

      10.1097/mpg.0000000000002053

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Breastfeeding regulates development of immune system through TGF-β in mice pups2018

    • Author(s)
      Sakaguchi Keita、Koyanagi Akemi、Kamachi Fumitaka、Harauma Akiko、Chiba Asako、Hisata Ken、Moriguchi Toru、Shimizu Toshiaki、Miyake Sachiko
    • Journal Title

      Pediatr Int

      Volume: 60(3) Issue: 3 Pages: 224-231

    • DOI

      10.1111/ped.13507

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 【炎症性腸疾患(第2版)-病因解明と診断・治療の最新知見-】 小児・高齢炎症性腸疾患の特徴と対応および炎症性腸疾患患者の妊娠への指導 小児炎症性腸疾患の疫学と現状および課題.2018

    • Author(s)
      清水俊明
    • Journal Title

      日本臨床

      Volume: 76(増) Pages: 483-489

    • Related Report
      2018 Research-status Report
  • [Journal Article] 【授乳と離乳-小児科医の基礎知識】 授乳・離乳の基本知識 授乳・離乳支援.2018

    • Author(s)
      東海林宏道,清水俊明.
    • Journal Title

      小児内科

      Volume: 50 Pages: 27-30

    • Related Report
      2018 Research-status Report
  • [Journal Article] Urinary prostaglandin D2 metabolite excretion during the first six months of life was significantly lower in breast-fed than formula-fed infants2017

    • Author(s)
      Shoji Hiromichi、Ikeda Naho、Kitamura Tomohiro、Suganuma Hiroki、Ohba Mai、Okuno Toshiaki、Yokomizo Takehiko、Shimizu Toshiaki
    • Journal Title

      Acta Paediatrica

      Volume: 107 Issue: 1 Pages: 95-100

    • DOI

      10.1111/apa.14068

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between insulin-like growth factor 1, leptin and ghrelin levels and catch-up growth in small for gestational age infants of 27-31 weeks during neonatal intensive care unit admission.2017

    • Author(s)
      Ohkawa N, Shoji H, Ikeda N, Suganuma H, Shimizu T.
    • Journal Title

      J Paediatr Child Health

      Volume: 53 Issue: 1 Pages: 62-67

    • DOI

      10.1111/jpc.13307

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rotavirus immunization: Global coverage and local barriers for implementation.2017

    • Author(s)
      Lo Vecchio A, Liguoro I, Dias JA, Berkley JA, Boey C, Cohen MB, Cruchet S, Salazar-Lindo E, Podder S, Sandhu B, Sherman PM, Shimizu T, Guarino A.
    • Journal Title

      Vaccine

      Volume: 35 Issue: 12 Pages: 1637-1644

    • DOI

      10.1016/j.vaccine.2017.01.082

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A pilot study of the effect of human breast milk on urinary metabolome analysis in infants.2017

    • Author(s)
      Shoji H, Taka H, Kaga N, Ikeda N, Kitamura T, Miura Y, Shimizu T.
    • Journal Title

      J Pediatr Endocrinol Metab

      Volume: 30 Pages: 939-946

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacological inhibition of Notch signaling suppresses food antigen-induced mucosal mast cell hyperplasia.2017

    • Author(s)
      Honjo A, Nakano N, Yamazaki S, Hara M, Uchida K, Kitaura J, Nishiyama C, Yagita H, Ohtsuka Y, Ogawa H, Okumura K, Shimizu T
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 139 Issue: 3 Pages: 987-996

    • DOI

      10.1016/j.jaci.2016.05.046

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 小児の健康と腸内細菌叢 出生後の免疫発達と腸内細菌叢の形成の関わりについて.2017

    • Author(s)
      坂口慶太,清水俊明.
    • Journal Title

      小児科臨床

      Volume: 70 Pages: 607-613

    • Related Report
      2017 Research-status Report
  • [Journal Article] 小児の下痢・便秘に対するプロバイオティクスのエビデンスと治療の位置づけ.2017

    • Author(s)
      佐藤真教,清水俊明.
    • Journal Title

      薬局

      Volume: 68 Pages: 55-59

    • Related Report
      2017 Research-status Report
  • [Journal Article] NICU入院中の管理 新生児壊死性腸炎の発症予防と治療 プロバイオティクスの使用方法.2017

    • Author(s)
      東海林宏道,久田研,清水俊明.
    • Journal Title

      周産期医学

      Volume: 47 Pages: 987-990

    • Related Report
      2017 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research Report
  • [Presentation] Effect of probiotics on neonates with HIE afterTH.2019

    • Author(s)
      Ikeda N, Awata K, Murano Y, Ohkawa N, Kantake M, Shoji H, Shimizu T.
    • Organizer
      The 14th World Congress of Perinatal Medicine, Istanbul, Turkey.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Body Mass Index in children born between 23 and 28 weeks of gestational age.2019

    • Author(s)
      Murano Y, Gilmour S, Shoji H, Ikeda N, Ohkawa N, Kantake M, Shimizu T.
    • Organizer
      The 14th World Congress of Perinatal Medicine, Istanbul, Turkey.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ビフィズス菌垂直伝達における新生児口腔内液の関与.2019

    • Author(s)
      荒井美輝,久田研,戸田一弥,清水金忠,東海林宏道,合阪幸三,清水俊明.
    • Organizer
      第16回日本小児栄養研究会,大阪.
    • Related Report
      2019 Research-status Report
  • [Presentation] 新生児低体温療法を要した児におけるプロバイオティクス使用の効果についての検討.2019

    • Author(s)
      松田明奈,西山樹,徳島香央里,中道伸彰,加護祐久,粟田健太郎,宮林和紀,齋藤暢知,池田奈帆,大川夏紀,寒竹正人,東海林宏道,清水俊明.
    • Organizer
      第122回日本小児科学会学術集会,金沢.
    • Related Report
      2019 Research-status Report
  • [Presentation] 新生児、早産・低出生体重児におけるプロバイオティクスの有用性.2018

    • Author(s)
      清水俊明.
    • Organizer
      シナジスインターネットライブセミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Choline-related metabolites influenced by feeding patterns in preterm and term infants.2018

    • Author(s)
      Shoji H, Watanabe A, Suganuma H, Shimizu T.
    • Organizer
      The 14th Asian Pan-Pacific Society of Pediatric Gastroenterology, Hepatology and Nutrition Meeting.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 極低出生体重児における3歳児の在胎週数別体格予後についての検討(周産期母子医療センターネットワーク10年まとめ事業).2018

    • Author(s)
      村野弥生,東海林宏道,渡邉晶子,淡路敦子,池田奈帆,大川夏紀,西﨑直人,久田研,寒竹正人,清水俊明.
    • Organizer
      第2回臨床DOHaDセミナー
    • Related Report
      2018 Research-status Report
  • [Presentation] 早産児の栄養管理のトピックス 5.microbiotaと予後.2017

    • Author(s)
      久田研,清水俊明.
    • Organizer
      第53回日本周産期・新生児医学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] 小児臨床栄養学 改訂第2版2018

    • Author(s)
      清水俊明.
    • Total Pages
      524
    • Publisher
      診断と治療社
    • ISBN
      9784787823397
    • Related Report
      2018 Research-status Report
  • [Remarks] 大腸最前線 小さく生まれた赤ちゃんの命の支え ビフィズス菌の直接投与で.

    • URL

      https://www.asahi.com/relife/article/13859021.

    • Related Report
      2020 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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