Effects of probiotics on gut mucosal immune response in low birth weight infants.

• Project/Area Number: 26461643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Juntendo University
• Principal Investigator: SHIMIZU Toshiaki 順天堂大学, 医学部, 教授 (30260889)
• Co-Investigator(Kenkyū-buntansha): 大塚 宜一 順天堂大学, 医学部, 客員准教授 (90338335) ; 東海林 宏道 順天堂大学, 医学(系)研究科(研究院), 准教授 (30365621)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: プロバイオティクス / 消化管粘膜 / 免疫応答 / 低出生体重児 / 母乳 / 腸内細菌

Outline of Final Research Achievements

To evaluate effects of Lactobacillus reuteri, Lactobacillus brevis and Bifidobacterium breve on the tight junction function of Caco-2 monolayer culture we established the measurement of TEER (transeptithelial electrical resistance) using volt-ohm meter. Newborn BALB/c mice were divided into dam-rearing pups and pups reared with milk substitute from 3-day-old using a hand-feeding system. In milk substitute-fed group, immune cells, such as the innate immune cells and CD8+T cells, were systemically more activated compared to those in dam-rearing group. We observed a colonization of Bifidobacterium. breve (M-16V) in low birth weight infants by administration of M-16V from soon after their birth detecting M16-V from stools of those infants ages at 1 month and 1 year. This finding shows the importance of early administration of probiotics in low birth weight infants.

Research Products

• [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
  • 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
  • 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 Issue: 9 Pages: 939-946
  • DOI: 10.1515/jpem-2017-0179
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 【腸内細菌叢と健康・疾患】 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
• [Journal Article] 【プロバイオティクス】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
• [Journal Article] 【超早産児の予後向上のための戦略【2】】 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
• [Journal Article] Influence of gestational age on serum incretin levels in preterm infants. (2016)
  • Author(s): Shoji H, Watanabe A, Ikeda N, Mori M, Kitamura T, Hisata K, Shimizu T.
  • Journal Title: J Dev Orig Health Dis Volume: 7 Issue: 6 Pages: 685-688
  • DOI: 10.1017/s2040174416000404
  • Peer Reviewed / Open Access
• [Journal Article] Clinically silent seizures in a neonate with tuberous sclerosis. (2016)
  • Author(s): Ikeno M, Okumura A, Abe S, Igarashi A, Hisata K, Shoji H, Shimizu T.
  • Journal Title: Pediatrics International Volume: 58 Issue: 1 Pages: 58-61
  • DOI: 10.1111/ped.12738
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ratio of docosahexaenoic acid and arachidonic acid in infant formula influences the fatty acid composition of the erythrocyte membrane in low-birth-weight infants. (2016)
  • Author(s): Kitamura T, Kitamura Y, Hamano H, Shoji H, Shimizu T, Shimizu T.
  • Journal Title: Ann Nutr Metab Volume: 68 Issue: 2 Pages: 103-112
  • DOI: 10.1159/000443024
  • Peer Reviewed / Open Access
• [Journal Article] Effect of PMX-DHP for sepsis due to ESBL-producing E. coli in an extremely low-birthweight infant. (2016)
  • Author(s): Nishizaki N, Nakagawa M, Hara S, Oda H, Kantake M, Obinata K, Uehara Y, Hiramatsu K, Shimizu T.
  • Journal Title: Pediatr Int Volume: 58 Issue: 5 Pages: 411-414
  • DOI: 10.1111/ped.12825
  • Peer Reviewed / Open Access
• [Journal Article] Reduced growth during early infancy in very low birth weight children with autism spectrum disorder. (2016)
  • Author(s): Ikejiri K, Hosozawa M, Mitomo S, Tanaka K, Shimizu T.
  • Journal Title: Early Hum Dev Volume: 98 Pages: 23-27
  • DOI: 10.1016/j.earlhumdev.2016.05.001
  • Peer Reviewed / Open Access
• [Journal Article] Effects of insulin-like growth factor-I during early postnatal period in intrauterine growth-restricted rats. (2015)
  • Author(s): Naho Ikeda, Hiromichi Shoji, Toshiaki Shimizu
  • Journal Title: Pediatrics International Volume: なし Issue: 5 Pages: 353-358
  • DOI: 10.1111/ped.12855
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An investigation into the vancomycin concentration in the cerebrospinal fluid due to vancomycin intraventricular administration in newborns: a study of 13 cases. (2015)
  • Author(s): Matsunaga N, Hisata K, Shimizu T.
  • Journal Title: Medicine Volume: 94 Issue: 22 Pages: e922-e922
  • DOI: 10.1097/md.0000000000000922
  • Peer Reviewed / Open Access
• [Journal Article] Profile of bile acids in fetal gallbladder and meconium using liquid chromatography-tandem mass spectrometry. (2015)
  • Author(s): Naritaka N, Suzuki M, Sato H, Takei H, Murai T, Kurosawa T, Iida T, Nittono H, Shimizu T.
  • Journal Title: Clin Chim Acta Volume: 446 Pages: 76-81
  • DOI: 10.1016/j.cca.2015.04.008
  • Peer Reviewed / Open Access
• [Journal Article] The Transcription Factor Ehf Is Involved in TGF-β-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells. (2015)
  • Author(s): Yamazaki S, Nakano N, Honjo A, Hara M, Maeda K, Nishiyama C, Kitaura J, Ohtsuka Y, Okumura K, Ogawa H, Shimizu T
  • Journal Title: Journal of immunology Volume: 195(7) Issue: 7 Pages: 3427-3435
  • DOI: 10.4049/jimmunol.1402856
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Critical Roles for PU.1, GATA1, and GATA2 in the Expression of Human FcεRI on Mast Cells: PU.1 and GATA1 Transactivate FCER1A, and GATA2 Transactivates FCER1A and MS4A2 (2014)
  • Author(s): Inage E, Kasakura K, Yashiro T, Suzuki R, Baba Y, Nakano N, Hara M, Tanabe A, Oboki K, Matsumoto K, Saito H, Niyonsaba F, Ohtsuka Y, Ogawa H, Okumura K, Shimizu T, and Nishiyama C
  • Journal Title: Journal of Immunology Volume: 192 Issue: 8 Pages: 3936-46
  • DOI: 10.4049/jimmunol.1302366
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Postnatal epigenetic modification of glucocorticoid receptor gene in preterm infants: a prospective study. (2014)
  • Author(s): Kantake M. Yoshitake H. Ishikawa H. Araki Y. Shimizu T.
  • Journal Title: BMJ Open Volume: - Issue: 7 Pages: e005318-e005318
  • DOI: 10.1136/bmjopen-2014-005318
  • Peer Reviewed / Open Access
• [Journal Article] Increased expression of CXCR3 axis components and matrix metalloproteinase in pediatric inflammatory bowel disease patients. (2014)
  • Author(s): Jimbo K, Ohtsuka Y, Kojima Y, Hosoi K, Ohbayashi N, Ikuse T, Aoyagi Y, Fujii T, Kudo T, Shimizu T.
  • Journal Title: Pediatr Int. Volume: 56 Issue: 6 Pages: 873-883
  • DOI: 10.1111/ped.12362
  • Peer Reviewed / Open Access
• [Journal Article] Fat emulsion given to very low-birthweight infants increases urinary L-FABP (2014)
  • Author(s): Suganuma H, Ikeda N, Ohkawa N, Nagata S, Shoji H, Shimizu T
  • Journal Title: Pediatr Int Volume: 56(2) Issue: 2 Pages: 207-10
  • DOI: 10.1111/ped.12223
  • Peer Reviewed / Open Access
• [Journal Article] Intestinal carriage of methicillin-resistant Staphylococcus aureus in nasal MRSA carriers hospitalized in the neonatal intensive care unit. (2014)
  • Author(s): Nakao A, Ito T, Han X, Lu YJ, Hisata K, Tsujiwaki A, Matsunaga N, Komatsu M, Hiramatsu K, Shimizu T.
  • Journal Title: Antimicrob Resist Infect Control Volume: 3 Issue: 1 Pages: 14-14
  • DOI: 10.1186/2047-2994-3-14
  • Peer Reviewed / Open Access
• [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
  • Invited
• [Presentation] Food sennsitive enteropathy. (2016)
  • Author(s): Shimizu T.
  • Organizer: 2016 KSPGHAN Symposium
  • Place of Presentation: Seol, Korea.
  • Int'l Joint Research / Invited
• [Presentation] NICUにおける血液培養と抗菌薬適正使用. (2016)
  • Author(s): 松永展明，久田研，清水俊明.
  • Organizer: 第61回日本新生児成育医学会学術集会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 動物モデルを用いた食物アレルギーの検討―Notchシグナルを介したマスト細胞の制御ー. (2016)
  • Author(s): 本庄明日香，中野信浩，山崎晋，山田啓迪，米山俊之，横倉友諒，稲毛英介，馬場洋介，森真理，大塚宜一，奥村康，清水俊明.
  • Organizer: 第2回東京小児アレルギー疾患研究会
  • Place of Presentation: 東京
  • Invited
• [Presentation] An analysis of gastrointestinal blood flow with doppler ultrasonography in children with food protein-induced enteropathy (2016)
  • Author(s): Jimbo K, Arai N, Kyoudo R, Sato M, Miyata E, Hosoi K, Matsumura S, Ohbayashi N, Ikuse T, Aoyagi Y, Fujii T, Kudo T, Asai N, Ohtsuka Y, Kono T, Shimizu T.
  • Organizer: The 5th World Congress of Pediatric Gastroenterology, Hepatology and Nutrition,
  • Place of Presentation: Montreal, Canada.
  • Int'l Joint Research
• [Presentation] Antigen-specific IgA plays an important role in mucosal immune response in allergic children: Measurement of secretory IgA and antigen-specific IgA. (2015)
  • Author(s): Baba Y, Yamazaki S, Inage E, Mori M, Kantake M, Ohtsuka Y, Shimizu T.
  • Organizer: The 23rd of the World Allergy Congress
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] The transcription factor Ehf is involved in TGF-β-induced suppression of FcεRI and c-Kit expression and FcεRI-mediated activation in mast cells. (2015)
  • Author(s): Yamazaki S, Nakano N, Honjo A, Hara M, Suzuki R, Ohtsuka Y, Okumura K, Ogawa H, Shimizu T.
  • Organizer: The 23rd of the World Allergy Congress
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-10-15
  • Int'l Joint Research
• [Presentation] 母乳が乳児の免疫能に与える影響の検討. (2015)
  • Author(s): 坂口慶太，小柳明美，蒲池史卓，原馬明子，千葉麻子，秋葉久弥，久田研，守口徹，三宅幸子，清水俊明.
  • Organizer: 第30回日本母乳哺育学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-04
• [Presentation] Food sensitive enteropathy. (2015)
  • Author(s): Shimizu T.
  • Organizer: 2015 annual National Conference of Chinese Pediatric Society
  • Place of Presentation: Xiamen, China.
  • Year and Date: 2015-09-24
  • Int'l Joint Research / Invited
• [Presentation] 小児領域におけるプロバイオティクスの有用性. (2015)
  • Author(s): 清水俊明.
  • Organizer: 第31回神奈川県小児肝・消化器疾患研究会
  • Place of Presentation: 横浜
  • Year and Date: 2015-09-09
  • Invited
• [Presentation] Increased expression of interleukin-26 in the mucosa of pediatric inflammatory bowel disease. (2015)
  • Author(s): Hosoi K, Kudo T, Obayashi N, Ikuse T, Jimbo K, Aoyagi Y, Fujii T, Ohtsuka Y, Shimizu T.
  • Organizer: The 11th Congress of the Asian Society for Pediatric Research & the 118th Annual Meeting of the Japan Pediatric Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2015-04-15
  • Int'l Joint Research