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Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 270301, 17 pages
http://dx.doi.org/10.1155/2013/270301
Review Article

Neonatal Immune Adaptation of the Gut and Its Role during Infections

ATIP-Avenir Group, INSERM U699, Université Paris Denis Diderot, Sorbonne Paris Cité, Site Xavier Bichat, 75018 Paris, France

Received 11 February 2013; Accepted 3 April 2013

Academic Editor: Philipp Henneke

Copyright © 2013 Emilie Tourneur and Cecilia Chassin. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. V. Hooper, T. Midwedt, and J. I. Gordon, “How host-microbial interactions shape the nutrient environment of the mammalian intestine,” Annual Review of Nutrition, vol. 22, pp. 283–307, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. B. Stecher, R. Robbiani, A. W. Walker et al., “Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota,” PLoS Biology, vol. 5, no. 10, pp. 2177–2189, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Endt, B. Stecher, S. Chaffron et al., “The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea,” PLoS Pathogens, vol. 6, no. 9, Article ID e1001097, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. E. Slack, S. Hapfelmeier, B. Stecher et al., “Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism,” Science, vol. 325, no. 5940, pp. 617–620, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. I. I. Ivanov, K. Atarashi, N. Manel et al., “Induction of intestinal Th17 cells by segmented filamentous bacteria,” Cell, vol. 139, no. 3, pp. 485–498, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. V. Gaboriau-Routhiau, S. Rakotobe, E. Lécuyer et al., “The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses,” Immunity, vol. 31, no. 4, pp. 677–689, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. N. Cerf-Bensussan and V. Gaboriau-Routhiau, “The immune system and the gut microbiota: friends or foes?” Nature Reviews Immunology, vol. 10, no. 10, pp. 735–744, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Atarashi, T. Tanoue, T. Shima et al., “Induction of colonic regulatory T cells by indigenous Clostridium species,” Science, vol. 331, no. 6015, pp. 337–341, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. W. S. Garrett, J. I. Gordon, and L. H. Glimcher, “Homeostasis and inflammation in the intestine,” Cell, vol. 140, no. 6, pp. 859–870, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. K. J. Maloy and F. Powrie, “Intestinal homeostasis and its breakdown in inflammatory bowel disease,” Nature, vol. 474, no. 7351, pp. 298–306, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. E. Cario, “Microbiota and innate immunity in intestinal inflammation and neoplasia,” Current Opinion in Gastroenterology, vol. 29, pp. 85–91, 2013. View at Publisher · View at Google Scholar
  12. A. Matsumoto, K. Hashimoto, T. Yoshioka, and H. Otani, “Occlusion and subsequent re-canalization in early duodenal development of human embryos: integrated organogenesis and histogenesis through a possible epithelial-mesenchymal interaction,” Anatomy and Embryology, vol. 205, no. 1, pp. 53–65, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. T. K. Noah, B. Donahue, and N. F. Shroyer, “Intestinal development and differentiation,” Experimental Cell Research, vol. 317, no. 9, pp. 2702–2710, 2011. View at Publisher · View at Google Scholar
  14. T. Savin, N. A. Kurpios, A. E. Shyer et al., “On the growth and form of the gut,” Nature, vol. 476, no. 7358, pp. 57–63, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. E. M. Braunstein, X. T. Qiao, B. Madison, K. Pinson, L. Dunbar, and D. L. Gumucio, “Villin: a marker for development of the epithelial pyloric border,” Developmental Dynamics, vol. 224, no. 1, pp. 90–102, 2002. View at Publisher · View at Google Scholar · View at Scopus
  16. A. S. Grosse, M. F. Pressprich, L. B. Curley, et al., “Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis,” Development, vol. 138, no. 20, pp. 4423–4432, 2011. View at Publisher · View at Google Scholar
  17. S. Hirano and K. Kataoka, “Histogenesis of the mouse jejunal mucosa, with special reference to proliferative cells and absorptive cells,” Archivum Histologicum Japonicum, vol. 49, no. 3, pp. 333–348, 1986. View at Scopus
  18. U. Gunther, J. A. Holloway, J. N. Gordon, et al., “Phenotypic characterization of CD37+ cells in developing human intestine and an analysis of their ability to differentiate into T cells,” Journal of Immunology, vol. 174, no. 9, pp. 5414–5422, 2005.
  19. N. Barker, J. H. van Es, J. Kuipers et al., “Identification of stem cells in small intestine and colon by marker gene Lgr5,” Nature, vol. 449, no. 7165, pp. 1003–1007, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Guilmeau, M. Flandez, L. Bancroft et al., “Intestinal deletion of Pofut1 in the mouse inactivates notch signaling and causes enterocolitis,” Gastroenterology, vol. 135, no. 3, pp. 849–860, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. G. C. Hansson, “Role of mucus layers in gut infection and inflammation,” Current Opinion in Microbiology, vol. 15, no. 1, pp. 57–62, 2012. View at Publisher · View at Google Scholar
  22. J. R. McDole, L. W. Wheeler, K. G. McDonald, et al., “Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine,” Nature, vol. 483, pp. 345–349, 2012. View at Publisher · View at Google Scholar
  23. M. Bogunovic, S. H. Davé, J. S. Tilstra et al., “Enteroendocrine cells express functional toll-like receptors,” American Journal of Physiology, vol. 292, no. 6, pp. G1770–G1783, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Ferri, L. C. U. Junqueira, L. F. Medeiros, and L. O. Medeiros, “Gross, microscopic and ultrastructural study of the intestinal tube of Xenodon merremii Wagler, 1824 (Ophidia),” Journal of Anatomy, vol. 121, no. 2, pp. 291–301, 1976. View at Scopus
  25. P. A. Hall, P. J. Coates, B. Ansari, and D. Hopwood, “Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis,” Journal of Cell Science, vol. 107, part 12, pp. 3569–3577, 1994. View at Scopus
  26. L. G. van der Flier and H. Clevers, “Stem cells, self-renewal, and differentiation in the intestinal epithelium,” Annual Review of Physiology, vol. 71, pp. 241–260, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Chassin, M. Kocur, J. Pott et al., “MiR-146a mediates protective innate immune tolerance in the neonate intestine,” Cell Host & Microbe, vol. 8, no. 4, pp. 358–368, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Harper, A. Mould, R. M. Andrews, E. K. Bikoff, and E. J. Robertson, “The transcriptional repressor Blimp1/Prdm1 regulates postnatal reprogramming of intestinal enterocytes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 26, pp. 10585–10590, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. V. Muncan, J. Heijmans, S. D. Krasinski, et al., “Blimp1 regulates the transition of neonatal to adult intestinal epithelium,” Nature Communications, vol. 2, p. 452, 2011. View at Publisher · View at Google Scholar
  30. A. G. Schepers, H. J. Snippert, D. E. Stange, et al., “Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas,” Science, vol. 337, pp. 730–735, 2012. View at Publisher · View at Google Scholar
  31. R. Romero, J. Nores, M. Mazor et al., “Microbial invasion of the amniotic cavity during term labor: prevalence and clinical significance,” Journal of Reproductive Medicine for the Obstetrician and Gynecologist, vol. 38, no. 7, pp. 543–548, 1993. View at Scopus
  32. D. B. DiGiulio, R. Romero, H. P. Amogan et al., “Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation,” PLoS One, vol. 3, no. 8, Article ID e3056, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. P. J. Giannone, B. L. Schanbacher, J. A. Bauer, and K. M. Reber, “Effects of prenatal lipopolysaccharide exposure on epithelial development and function in newborn rat intestine,” Journal of Pediatric Gastroenterology and Nutrition, vol. 43, no. 3, pp. 284–290, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. N. Blümer, P. I. Pfefferle, and H. Renz, “Development of mucosal immune function in the intrauterine and early postnatal environment,” Current Opinion in Gastroenterology, vol. 23, no. 6, pp. 655–660, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. M. S. Cilieborg, M. Schmidt, K. Skovgaard, et al., “Fetal lipopolysaccharide exposure modulates diet-dependent gut maturation and sensitivity to necrotising enterocolitis in pre-term pigs,” British Journal of Nutrition, vol. 106, no. 6, pp. 852–861, 2011. View at Publisher · View at Google Scholar
  36. R. W. Schaedler, R. Dubos, and R. Costello, “The development of the bacterial flora in the gastrointestinal tract of mice,” The Journal of Experimental Medicine, vol. 122, no. 1, pp. 59–66, 1965. View at Publisher · View at Google Scholar
  37. K. Hirayama, K. Miyaji, S. Kawamura, K. Itoh, E. Takahashi, and T. Mitsuoka, “Development of intestinal flora of human-flora-associated (HFA) mice in the intestine of their offspring,” Experimental Animals, vol. 44, no. 3, pp. 219–222, 1995. View at Scopus
  38. S. Stockinger, M. W. Hornef, and C. Chassin, “Establishment of intestinal homeostasis during the neonatal period,” Cellular and Molecular Life Sciences, vol. 68, no. 22, pp. 3699–3712, 2011. View at Publisher · View at Google Scholar
  39. P. A. Scholtens, R. Oozeer, R. Martin, K. B. Amor, and J. Knol, “The early settlers: intestinal microbiology in early life,” Annual Review of Food Science and Technology, vol. 3, pp. 425–447, 2012. View at Publisher · View at Google Scholar
  40. V. Tremaroli and F. Bäckhed, “Functional interactions between the gut microbiota and host metabolism,” Nature, vol. 489, pp. 242–249, 2012. View at Publisher · View at Google Scholar
  41. S. El Aidy, G. Hooiveld, V. Tremaroli, F. Bäckhed, and M. Kleerebezem, “The gut microbiota and mucosal homeostasis: colonized at birth or at adulthood, does it matter?” Gut Microbes, vol. 4, no. 2, pp. 118–124, 2013. View at Publisher · View at Google Scholar
  42. M. G. Dominguez-Bello, E. K. Costello, M. Contreras et al., “Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 26, pp. 11971–11975, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Eggesbø, B. Moen, S. Peddada et al., “Development of gut microbiota in infants not exposed to medical interventions,” APMIS, vol. 119, no. 1, pp. 17–35, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. M. M. Grönlund, O. P. Lehtonen, E. Eerola, and P. Kero, “Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery,” Journal of Pediatric Gastroenterology and Nutrition, vol. 28, no. 1, pp. 19–25, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Matsumiya, N. Kato, K. Watanabe, and H. Kato, “Molecular epidemiological study of vertical transmission of vaginal Lactobacillus species from mothers to newborn infants in Japanese, by arbitrarily primed polymerase chain reaction,” Journal of Infection and Chemotherapy, vol. 8, no. 1, pp. 43–49, 2002. View at Scopus
  46. R. Mändar and M. Mikelsaar, “Transmission of mother's microflora to the newborn at birth,” Biology of the Neonate, vol. 69, no. 1, pp. 30–35, 1996. View at Scopus
  47. S. Fanaro, R. Chierici, P. Guerrini, and V. Vigi, “Intestinal microflora in early infancy: composition and development,” Acta Paediatrica, International Journal of Paediatrics, Supplement, vol. 91, no. 441, pp. 48–55, 2003. View at Scopus
  48. E. Decker, M. Hornef, and S. Stockinger, “Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children,” Gut Microbes, vol. 2, no. 2, pp. 91–98, 2011. View at Scopus
  49. E. K. Costello, C. L. Lauber, M. Hamady, N. Fierer, J. I. Gordon, and R. Knight, “Bacterial community variation in human body habitats across space and time,” Science, vol. 326, no. 5960, pp. 1694–1697, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. J. E. Koenig, A. Spor, N. Scalfone et al., “Succession of microbial consortia in the developing infant gut microbiome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, supplement 1, pp. 4578–4585, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. E. G. Zoetendal, K. Ben-Amor, A. D. L. Akkermans, T. Abee, and W. M. de Vos, “DNA isolation protocols affect the detection limit of PCR approaches of bacteria in samples from the human gastrointestinal tract,” Systematic and Applied Microbiology, vol. 24, no. 3, pp. 405–410, 2001. View at Scopus
  52. P. J. Turnbaugh, M. Hamady, T. Yatsunenko et al., “A core gut microbiome in obese and lean twins,” Nature, vol. 457, no. 7228, pp. 480–484, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. C. L. Bevins and N. H. Salzman, “The potter's wheel: the host's role in sculpting its microbiota,” Cellular and Molecular Life Sciences, vol. 68, no. 22, pp. 3675–3685, 2011. View at Publisher · View at Google Scholar
  54. F. Bäckhed, R. E. Ley, J. L. Sonnenburg, D. A. Peterson, and J. I. Gordon, “Host-bacterial mutualism in the human intestine,” Science, vol. 307, no. 5717, pp. 1915–1920, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. C. V. Srikanth and B. A. McCormick, “Interactions of the intestinal epithelium with the pathogen and the indigenous microbiota: a three-way crosstalk,” Interdisciplinary Perspectives on Infectious Diseases, vol. 2008, Article ID 626827, 14 pages, 2008. View at Publisher · View at Google Scholar
  56. P. Brandtzaeg, I. N. Farstad, G. Haraldsen, and F. L. Jahnsen, “Cellular and molecular mechanisms for induction of mucosal immunity,” Developments in Biological Standardization, vol. 92, pp. 93–108, 1998. View at Scopus
  57. H. Renz, P. Brandtzaeg, and M. Hornef, “The impact of perinatal immune development on mucosal homeostasis and chronic inflammation,” Nature Reviews Immunology, vol. 12, pp. 9–23, 2012.
  58. R. D. Fusunyan, N. N. Nanthakumar, M. E. Baldeon, and W. A. Walker, “Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes,” Pediatric Research, vol. 49, no. 4, pp. 589–593, 2001. View at Scopus
  59. M. T. Abreu, “Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function,” Nature Reviews Immunology, vol. 10, no. 2, pp. 131–143, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. K. Geddes, S. Rubino, C. Streutker et al., “Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model,” Infection and Immunity, vol. 78, no. 12, pp. 5107–5115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. A. H. Broquet, Y. Hirata, C. S. McAllister, and M. F. Kagnoff, “RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium,” Journal of Immunology, vol. 186, no. 3, pp. 1618–1626, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Pott, T. Mahlakõiv, M. Mordstein et al., “IFN-λ determines the intestinal epithelial antiviral host defense,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 19, pp. 7944–7949, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. R. Kajino-Sakamoto, M. Inagaki, E. Lippert et al., “Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis,” Journal of Immunology, vol. 181, no. 2, pp. 1143–1152, 2008. View at Scopus
  64. A. Nenci, C. Becker, A. Wullaert et al., “Epithelial NEMO links innate immunity to chronic intestinal inflammation,” Nature, vol. 446, no. 7135, pp. 557–561, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. J. L. Round and S. K. Mazmanian, “The gut microbiota shapes intestinal immune responses during health and disease,” Nature Reviews Immunology, vol. 9, no. 5, pp. 313–323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. I. I. Ivanov and K. Honda, “Intestinal commensal microbes as immune modulators,” Cell Host & Microbe, vol. 12, pp. 496–508, 2012. View at Publisher · View at Google Scholar
  67. D. Bouskra, C. Brézillon, M. Bérard et al., “Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis,” Nature, vol. 456, no. 7221, pp. 507–510, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. L. V. Hooper, T. S. Stappenbeck, C. V. Hong, and J. I. Gordon, “Angiogenins: a new class of microbicidal proteins involved in innate immunity,” Nature Immunology, vol. 4, no. 3, pp. 269–273, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. H. L. Cash, C. V. Whitham, C. L. Behrendt, and L. V. Hooper, “Symbiotic bacteria direct expression of an intestinal bactericidal lectin,” Science, vol. 313, no. 5790, pp. 1126–1130, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. A. J. Macpherson and T. Uhr, “Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria,” Science, vol. 303, no. 5664, pp. 1662–1665, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. S. K. Mazmanian, C. H. Liu, A. O. Tzianabos, and D. L. Kasper, “An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system,” Cell, vol. 122, no. 1, pp. 107–118, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. J. L. Coombes and F. Powrie, “Dendritic cells in intestinal immune regulation,” Nature Reviews Immunology, vol. 8, no. 6, pp. 435–446, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. N. Shulzhenko, A. Morgun, W. Hsiao, et al., “Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut,” Nature Medicine, vol. 17, pp. 1585–1593, 2011. View at Publisher · View at Google Scholar
  74. S. Fukuda, H. Toh, K. Hase et al., “Bifidobacteria can protect from enteropathogenic infection through production of acetate,” Nature, vol. 469, no. 7331, pp. 543–549, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. J. L. Round, S. M. Lee, J. Li et al., “The toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota,” Science, vol. 332, no. 6032, pp. 974–977, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. C. Atuma, V. Strugala, A. Allen, and L. Holm, “The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo,” American Journal of Physiology, vol. 280, no. 5, pp. G922–G929, 2001. View at Scopus
  77. D. Ambort, S. van der Post, M. E. V. Johansson et al., “Function of the CysD domain of the gel-forming MUC2 mucin,” Biochemical Journal, vol. 436, no. 1, pp. 61–70, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. M. E. V. Johansson, M. Phillipson, J. Petersson, A. Velcich, L. Holm, and G. C. Hansson, “The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 39, pp. 15064–15069, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. M. E. V. Johansson, J. M. Larsson, and G. C. Hansson, “The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, supplement 1, pp. 4659–4665, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. M. E. V. Johansson, J. K. Gustafsson, K. E. Sjöberg et al., “Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model,” PLoS One, vol. 5, no. 8, Article ID e12238, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. M. van der Sluis, B. A. E. de Koning, A. C. J. M. de Bruijn et al., “Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection,” Gastroenterology, vol. 131, no. 1, pp. 117–129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. D. K. Meyerholz, T. J. Stabel, M. R. Ackermann, S. A. Carlson, B. D. Jones, and J. Pohlenz, “Early epithelial invasion by Salmonella enterica serovar Typhimurium DT104 in the swine ileum,” Veterinary Pathology, vol. 39, no. 6, pp. 712–720, 2002. View at Scopus
  83. G. Nikitas, C. Deschamps, O. Disson, et al., “Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin,” The Journal of Experimental Medicine, vol. 208, no. 11, pp. 2263–2277, 2011. View at Publisher · View at Google Scholar
  84. C. Crosnier, D. Stamataki, and J. Lewis, “Organizing cell renewal in the intestine: stem cells, signals and combinatorial control,” Nature Reviews Genetics, vol. 7, no. 5, pp. 349–359, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. C. P. Sodhi, M. D. Neal, R. Siggers, et al., “Intestinal epithelial toll-like receptor 4 regulates goblet cell development and is required for necrotizing enterocolitis in mice,” Gastroenterology, vol. 143, no. 3, pp. 708–718, 2012. View at Publisher · View at Google Scholar
  86. B. Liu, Z. Yu, C. Chen, D. E. Kling, and D. S. Newburg, “Human milk mucin 1 and mucin 4 inhibit Salmonella enterica serovar Typhimurium invasion of human intestinal epithelial cells in vitro,” Journal of Nutrition, vol. 142, pp. 1504–1509, 2012. View at Publisher · View at Google Scholar
  87. A. Marcobal, M. Barboza, E. D. Sonnenburg, et al., “Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways,” Cell Host & Microbe, vol. 10, no. 5, pp. 507–514, 2011. View at Publisher · View at Google Scholar
  88. D. A. Shifrin, R. E. McConnell, R. Nambiar, J. N. Higginbotham, R. J. Coffey, and M. J. Tyska, “Enterocyte microvillus-derived vesicles detoxify bacterial products and regulate epithelial-microbial interactions,” Current Biology, vol. 22, no. 7, pp. 627–631, 2012. View at Publisher · View at Google Scholar
  89. C. U. Duerr, N. H. Salzman, A. Dupont et al., “Control of intestinal Nod2-mediated peptidoglycan recognition by epithelium-associated lymphocytes,” Mucosal Immunology, vol. 4, no. 3, pp. 325–334, 2011. View at Publisher · View at Google Scholar · View at Scopus
  90. Y. Lai and R. L. Gallo, “AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense,” Trends in Immunology, vol. 30, no. 3, pp. 131–141, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. N. H. Salzman, M. A. Underwood, and C. L. Bevins, “Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa,” Seminars in Immunology, vol. 19, no. 2, pp. 70–83, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. C. L. Bevins and N. H. Salzman, “Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis,” Nature Reviews Microbiology, vol. 9, no. 5, pp. 356–368, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. M. W. Hornef, K. Pütsep, J. Karlsson, E. Refai, and M. Andersson, “Increased diversity of intestinal antimicrobial peptides by covalent dimer formation,” Nature Immunology, vol. 5, no. 8, pp. 836–843, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. N. H. Salzman, K. Hung, D. Haribhai et al., “Enteric defensins are essential regulators of intestinal microbial ecology,” Nature Immunology, vol. 11, no. 1, pp. 76–83, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. C. L. Wilson, A. J. Ouellette, D. P. Satchell et al., “Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense,” Science, vol. 286, no. 5437, pp. 113–117, 1999. View at Publisher · View at Google Scholar · View at Scopus
  96. N. H. Salzman, D. Ghosh, K. M. Huttner, Y. Paterson, and C. L. Bevins, “Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin,” Nature, vol. 422, no. 6931, pp. 522–526, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. R. Inoue, T. Tsuruta, I. Nojima, K. Nakayama, T. Tsukahara, and T. Yajima, “Postnatal changes in the expression of genes for cryptdins 1-6 and the role of luminal bacteria in cryptdin gene expression in mouse small intestine,” FEMS Immunology and Medical Microbiology, vol. 52, no. 3, pp. 407–416, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Ménard, V. Förster, M. Lotz, et al., “Developmental switch of intestinal antimicrobial peptide expression,” The Journal of Experimental Medicine, vol. 205, no. 1, pp. 183–193, 2008.
  99. Y. Kai-Larsen, G. Bergsson, G. H. Gudmundsson et al., “Antimicrobial components of the neonatal gut affected upon colonization,” Pediatric Research, vol. 61, no. 5, pp. 530–536, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. N. Burger-van Paassen, L. M. Loonen, J. Witte-Bouma, et al., “Mucin Muc2 deficiency and weaning influences the expression of the innate defense genes Reg3β, Reg3γ and angiogenin-4,” PLoS One, vol. 7, Article ID e38798, 2012.
  101. S. Vaishnava, M. Yamamoto, K. M. Severson, et al., “The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine,” Science, vol. 334, no. 6053, pp. 255–258, 2011. View at Publisher · View at Google Scholar
  102. S. L. Sanos, V. L. Bui, A. Mortha et al., “RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells,” Nature Immunology, vol. 10, no. 1, pp. 83–91, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. R. E. Lehotzky, C. L. Partch, S. Mukherjee, et al., “Molecular basis for peptidoglycan recognition by a bactericidal lectin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 17, pp. 7722–7727, 2010. View at Publisher · View at Google Scholar
  104. A. L. Frantz, E. W. Rogier, C. R. Weber, et al., “Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides,” Mucosal Immunology, vol. 5, pp. 501–512, 2012. View at Publisher · View at Google Scholar
  105. K. Brandl, G. Plitas, B. Schnabl, R. P. DeMatteo, and E. G. Pamer, “MyD88-mediated signals induce the bactericidal lectin RegIIIγ and protect mice against intestinal Listeria monocytogenes infection,” Journal of Experimental Medicine, vol. 204, no. 8, pp. 1891–1900, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. N. L. Harris, I. Spoerri, J. F. Schopfer et al., “Mechanisms of neonatal mucosal antibody protection,” Journal of Immunology, vol. 177, no. 9, pp. 6256–6262, 2006. View at Scopus
  107. J. L. Siggers, M. V. Ostergaard, R. H. Siggers, et al., “Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates,” American Journal of Physiology, 2013. View at Publisher · View at Google Scholar
  108. R. Garofalo, “Cytokines in human milk,” Journal of Pediatrics, vol. 156, no. 2, pp. S36–S40, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. A. S. Goldman, “The immune system of human milk: antimicrobial, antiinflammatory and immunomodulating properties,” Pediatric Infectious Disease Journal, vol. 12, no. 8, pp. 664–671, 1993. View at Scopus
  110. A. G. Cummins and F. M. Thompson, “Postnatal changes in mucosal immune response: a physiological perspective of breast feeding and weaning,” Immunology and Cell Biology, vol. 75, no. 5, pp. 419–429, 1997. View at Scopus
  111. N. Kosaka, H. Izumi, K. Sekine, and T. Ochiya, “MicroRNA as a new immune-regulatory agent in breast milk,” Silence, vol. 1, no. 1, article 7, 2010. View at Publisher · View at Google Scholar · View at Scopus
  112. C. L. Wagner, S. N. Taylor, and D. Johnson, “Host factors in amniotic fluid and breast milk that contribute to gut maturation,” Clinical Reviews in Allergy and Immunology, vol. 34, no. 2, pp. 191–204, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. Y. Liao and B. Lönnerdal, “MiR-584 mediates post-transcriptional expression of lactoferrin receptor in Caco-2 cells and in mouse small intestine during the perinatal period,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 8, pp. 1363–1369, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. D. A. Sela, J. Chapman, A. Adeuya et al., “The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 48, pp. 18964–18969, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. M. J. Gillespie, D. Stanley, H. Chen, et al., “Functional similarities between pigeon ‘milk’ and mammalian milk: induction of immune gene expression and modification of the microbiota,” PLoS One, vol. 7, Article ID e48363, 2012.
  116. P. F. Perez, J. Doré, M. Leclerc et al., “Bacterial imprinting of the neonatal immune system: lessons from maternal cells?” Pediatrics, vol. 119, no. 3, pp. e724–e732, 2007. View at Publisher · View at Google Scholar · View at Scopus
  117. A. Donnet-Hughes, P. F. Perez, J. Doré et al., “Potential role of the intestinal microbiota of the mother in neonatal immune education,” Proceedings of the Nutrition Society, vol. 69, no. 3, pp. 407–415, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. D. Comito and C. Romano, “Dysbiosis in the pathogenesis of pediatric inflammatory bowel diseases,” International Journal of Inflammation, vol. 2012, Article ID 687143, 7 pages, 2012. View at Publisher · View at Google Scholar
  119. C. Lupp, M. L. Robertson, M. E. Wickham et al., “Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae,” Cell Host & Microbe, vol. 2, no. 2, pp. 119–129, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. G. E. Galán, J. Pace, and M. J. Hayman, “Involvement of the epidermal growth factor receptor in the invasion of cultured mammalian cells by Salmonella typhimurium,” Nature, vol. 357, no. 6379, pp. 588–589, 1992. View at Publisher · View at Google Scholar · View at Scopus
  121. C. U. Duerr, S. F. Zenk, C. Chassin et al., “O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells,” PLoS Pathogens, vol. 5, no. 9, Article ID e1000567, 2009. View at Publisher · View at Google Scholar · View at Scopus
  122. M. P. Sherman, “New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention,” Clinics in Perinatology, vol. 37, no. 3, pp. 565–579, 2010. View at Publisher · View at Google Scholar · View at Scopus
  123. M. H. Ruchaud-Sparagano, S. Mühlen, P. Dean, and B. Kenny, “The enteropathogenic E. coli (EPEC) Tir effector inhibits NF-κB activity by targeting TNFα receptor-associated factors,” PLoS Pathogens, vol. 7, Article ID e1002414, 2011. View at Publisher · View at Google Scholar
  124. R. J. Anand, C. L. Leaphart, K. P. Mollen, and D. J. Hackam, “The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis,” Shock, vol. 27, no. 2, pp. 124–133, 2007. View at Publisher · View at Google Scholar · View at Scopus
  125. S. Nikkari, I. J. McLaughlin, W. Bi, D. E. Dodge, and D. A. Relman, “Does blood of healthy subjects contain bacterial ribosomal DNA?” Journal of Clinical Microbiology, vol. 39, no. 5, pp. 1956–1959, 2001. View at Publisher · View at Google Scholar · View at Scopus
  126. J. O. Gebbers and J. A. Laissue, “Bacterial translocation in the normal human appendix parallels the development of the local immune system,” Annals of the New York Academy of Sciences, vol. 1029, pp. 337–343, 2004. View at Publisher · View at Google Scholar · View at Scopus
  127. D. H. Shim, S. Ryu, and M. N. Kweon, “Defensins play a crucial role in protecting mice against oral Shigella flexneri infection,” Biochemical and Biophysical Research Communications, vol. 401, no. 4, pp. 554–560, 2010. View at Publisher · View at Google Scholar · View at Scopus
  128. J. Pott, S. Stockinger, N. Torow, et al., “Age-dependent TLR3 expression of the intestinal epithelium contributes to rotavirus susceptibility,” PLoS Pathogens, vol. 8, no. 5, Article ID e1002670, 2012.
  129. S. J. Rhee, W. A. Walker, and B. J. Cherayil, “Developmentally regulated intestinal expression of IFN-γ and its target genes and the age-specific response to enteric Salmonella infection,” Journal of Immunology, vol. 175, no. 2, pp. 1127–1136, 2005. View at Scopus
  130. I. Nupponen, S. Andersson, A. L. Järvenpää, H. Kautiainen, and H. Repo, “Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis,” Pediatrics, vol. 108, no. 1, p. E12, 2001. View at Scopus
  131. J. E. Lawn, S. Cousens, and J. Zupan, “4 million neonatal deaths: when? Where? Why?” The Lancet, vol. 365, no. 9462, pp. 891–900, 2005. View at Publisher · View at Google Scholar · View at Scopus
  132. B. J. Stoll, N. I. Hansen, R. D. Higgins et al., “Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of Gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003,” Pediatric Infectious Disease Journal, vol. 24, no. 7, pp. 635–639, 2005. View at Publisher · View at Google Scholar · View at Scopus
  133. R. S. Hotchkiss, K. W. Tinsley, P. E. Swanson et al., “Depletion of dendritic cells, but not macrophages, in patients with sepsis,” Journal of Immunology, vol. 168, no. 5, pp. 2493–2500, 2002. View at Scopus
  134. J. L. Wynn, P. O. Seumpia, R. D. Winfield et al., “Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists,” Blood, vol. 112, no. 5, pp. 1750–1758, 2008. View at Publisher · View at Google Scholar · View at Scopus
  135. C. Härtel, C. Hemmelmann, K. Faust, et al., “Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants,” Critical Care Medicine, vol. 39, no. 5, pp. 1190–1195, 2011. View at Publisher · View at Google Scholar
  136. J. I. Kawada, H. Kimura, Y. Ito et al., “Evaluation of systemic inflammatory responses in neonates with herpes simplex virus infection,” Journal of Infectious Diseases, vol. 190, no. 3, pp. 494–498, 2004. View at Publisher · View at Google Scholar · View at Scopus
  137. M. A. Verboon-Maciolek, T. G. Krediet, L. J. Gerards, A. Fleer, and T. M. van Loon, “Clinical and epidemiologic characteristics of viral infections in a neonatal intensive care unit during a 12-year period,” Pediatric Infectious Disease Journal, vol. 24, no. 10, pp. 901–904, 2005. View at Publisher · View at Google Scholar · View at Scopus
  138. M. Paolucci, M. P. Landini, and V. Sambri, “How can the microbiologist help in diagnosing neonatal sepsis?” International Journal of Pediatrics, vol. 2012, Article ID 120139, 14 pages, 2012. View at Publisher · View at Google Scholar
  139. G. Klinger, I. Levy, L. Sirota, V. Boyko, B. Reichman, and L. Lerner-Geva, “Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants,” American Journal of Obstetrics and Gynecology, vol. 201, no. 1, pp. e31–e36, 2009. View at Publisher · View at Google Scholar · View at Scopus
  140. B. J. Stoll, N. I. Hansen, P. J. Sánchez et al., “Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues,” Pediatrics, vol. 127, no. 5, pp. 817–826, 2011. View at Publisher · View at Google Scholar · View at Scopus
  141. J. Morinis, J. Shah, P. Murthy, and M. Fulford, “Horizontal transmission of group B streptococcus in a neonatal intensive care unit,” Paediatr Child Health, vol. 16, pp. e48–e50, 2011.
  142. J. H. Jiang, N. C. Chiu, F. Y. Huang et al., “Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset,” Journal of Microbiology, Immunology and Infection, vol. 37, no. 5, pp. 301–306, 2004. View at Scopus
  143. C. M. Healy, D. L. Palazzi, M. S. Edwards, J. R. Campbell, and C. J. Baker, “Features of invasive staphylococcal disease in neonates,” Pediatrics, vol. 114, no. 4, pp. 953–961, 2004. View at Publisher · View at Google Scholar · View at Scopus
  144. O. Levy, K. A. Zarember, R. M. Roy, C. Cywes, P. J. Godowski, and M. R. Wessels, “Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-α induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848,” Journal of Immunology, vol. 173, no. 7, pp. 4627–4634, 2004. View at Scopus
  145. E. Förster-Waldl, K. Sadeghi, D. Tamandl et al., “Monocyte toll-like receptor 4 expression and LPS-induced cytokine production increase during gestational aging,” Pediatric Research, vol. 58, no. 1, pp. 121–124, 2005. View at Publisher · View at Google Scholar · View at Scopus
  146. M. Otto, “Virulence factors of the coagulase-negative staphylococci,” Frontiers in Bioscience, vol. 9, pp. 841–863, 2004. View at Scopus
  147. C. Vuong, J. M. Voyich, E. R. Fischer et al., “Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system,” Cellular Microbiology, vol. 6, no. 3, pp. 269–275, 2004. View at Publisher · View at Google Scholar · View at Scopus
  148. S. Kocianova, C. Vuong, Y. Yao et al., “Key role of poly-γ-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis,” Journal of Clinical Investigation, vol. 115, no. 3, pp. 688–694, 2005. View at Publisher · View at Google Scholar · View at Scopus
  149. H. N. Granslo, C. Klingenberg, E. A. Fredheim, G. Acharya, T. E. Mollnes, and T. Flægstad, “Staphylococcus epidermidis biofilms induce lower complement activation in neonates as compared with adults,” Pediatric Research, vol. 73, no. 3, pp. 294–300, 2013. View at Publisher · View at Google Scholar
  150. M. P. Venkatesh and L. Rong, “Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis,” Journal of Medical Microbiology, vol. 57, no. 9, pp. 1113–1121, 2008. View at Publisher · View at Google Scholar · View at Scopus
  151. K. S. Doran and V. Nizet, “Molecular pathogenesis of neonatal group B streptococcal infection: no longer in its infancy,” Molecular Microbiology, vol. 54, no. 1, pp. 23–31, 2004. View at Publisher · View at Google Scholar · View at Scopus
  152. P. Henneke and R. Berner, “Interaction of neonatal phagocytes with group B streptococcus: recognition and Response,” Infection and Immunity, vol. 74, no. 6, pp. 3085–3095, 2006. View at Publisher · View at Google Scholar · View at Scopus
  153. S. Kenzel, S. Santos-Sierra, S. D. Deshmukh et al., “Role of p38 and early growth response factor 1 in the macrophage response to group B streptococcus,” Infection and Immunity, vol. 77, no. 6, pp. 2474–2481, 2009. View at Publisher · View at Google Scholar · View at Scopus
  154. P. Henneke, S. Dramsi, G. Mancuso, et al., “Lipoproteins are critical TLR2 activating toxins in group B streptococcal sepsis,” Journal of Immunology, vol. 180, no. 9, pp. 6149–6158, 2008.
  155. S. D. Deshmukh, B. Kremer, M. Freudenberg, S. Bauer, D. T. Golenbock, and P. Henneke, “Macrophages recognize streptococci through bacterial single-stranded RNA,” EMBO Reports, vol. 12, no. 1, pp. 71–76, 2011. View at Publisher · View at Google Scholar · View at Scopus
  156. S. D. Deshmukh, S. Müller, K. Hese, et al., “NO is a macrophage autonomous modifier of the cytokine response to streptococcal single-stranded RNA,” The Journal of Immunology, vol. 188, pp. 774–780, 2012. View at Publisher · View at Google Scholar
  157. A. Costa, R. Gupta, G. Signorino, et al., “Activation of the NLRP3 inflammasome by group B streptococci,” The Journal of Immunology, vol. 188, pp. 1953–1960, 2012. View at Publisher · View at Google Scholar
  158. F. Cekmez, C. Tayman, C. Saglam, et al., “Well-known but rare pathogen in neonates: Listeria monocytogenes,” European Review for Medical and Pharmacological Sciences, vol. 16, supplement 4, pp. 58–61, 2012.
  159. W. Dai, G. Köhler, and F. Brombacher, “Both innate and acquired immunity to Listeria monocytogenes infection are increased in IL-10-deficient mice,” Journal of Immunology, vol. 158, no. 5, pp. 2259–2267, 1997. View at Scopus
  160. F. Genovese, G. Mancuso, M. Cuzzola et al., “Role of IL-10 in a neonatal mouse listeriosis model,” Journal of Immunology, vol. 163, no. 5, pp. 2777–2782, 1999. View at Scopus
  161. T. Dolowschiak, C. Chassin, S. B. Mkaddem et al., “Potentiation of epithelial innate host responses by intercellular communication,” PLoS Pathogens, vol. 6, no. 11, Article ID e1001194, 2010. View at Publisher · View at Google Scholar · View at Scopus
  162. Y. Iizumi, H. Sagara, Y. Kabe et al., “The enteropathogenic E. coli effector EspB facilitates microvillus effacing and antiphagocytosis by inhibiting myosin function,” Cell Host & Microbe, vol. 2, no. 6, pp. 383–392, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. R. P. Fagan, M. A. Lambert, and S. G. J. Smith, “The Hek outer membrane protein of Escherichia coli strain RS218 binds to proteoglycan and utilizes a single extracellular loop for adherence, invasion, and autoaggregation,” Infection and Immunity, vol. 76, no. 3, pp. 1135–1142, 2008. View at Publisher · View at Google Scholar · View at Scopus
  164. R. Yang, K. Miki, N. Oksala et al., “Bile high-mobility group box 1 contributes to gut barrier dysfunction in experimental endotoxemia,” American Journal of Physiology, vol. 297, no. 2, pp. R362–R369, 2009. View at Publisher · View at Google Scholar · View at Scopus
  165. J. K. Actor, S. A. Hwang, and M. L. Kruzel, “Lactoferrin as a natural immune modulator,” Current Pharmaceutical Design, vol. 15, no. 17, pp. 1956–1973, 2009. View at Publisher · View at Google Scholar · View at Scopus
  166. Y. Kawasaki, S. Tazume, K. Shimizu et al., “Inhibitory effects of bovine lactoferrin on the adherence of enterotoxigenic Escherichia coli to host cells,” Bioscience, Biotechnology and Biochemistry, vol. 64, no. 2, pp. 348–354, 2000. View at Scopus
  167. R. Sharma, J. J. Tepas, M. L. Hudak et al., “Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis,” Journal of Pediatric Surgery, vol. 42, no. 3, pp. 454–461, 2007. View at Publisher · View at Google Scholar · View at Scopus
  168. C. Chassin, C. Hempel, S. Stockinger, et al., “MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small intestine against ischemia/reperfusion injury,” EMBO Molecular Medicine, vol. 4, no. 12, pp. 1308–1319, 2012. View at Publisher · View at Google Scholar
  169. L. Leigh, B. J. Stoll, M. Rahman, and J. McGowan, “Pseudomonas aeruginosa infection in very low birth weight infants: a case- control study,” Pediatric Infectious Disease Journal, vol. 14, no. 5, pp. 367–371, 1995. View at Scopus
  170. J. Neu, “Gastrointestinal maturation and implications for infant feeding,” Early Human Development, vol. 83, no. 12, pp. 767–775, 2007. View at Publisher · View at Google Scholar · View at Scopus
  171. J. L. Wynn, J. Neu, L. L. Moldawer, and O. Levy, “Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis,” Journal of Perinatology, vol. 29, no. 2, pp. 79–88, 2009. View at Publisher · View at Google Scholar · View at Scopus
  172. V. Mai, R. M. Torrazza, M. Ukhanova, et al., “Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants,” PLoS One, vol. 8, no. 1, Article ID e52876, 2013. View at Publisher · View at Google Scholar
  173. J. C. Madan, R. C. Salari, D. Saxena, et al., “Gut microbial colonisation in premature neonates predicts neonatal sepsis,” Archives of Disease in Childhood. Fetal and Neonatal Edition, vol. 97, no. 6, pp. F456–F462, 2012. View at Publisher · View at Google Scholar
  174. J. S. Ayres, N. J. Trinidad, and R. E. Vance, “Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota,” Nature Medicine, vol. 18, pp. 799–806, 2012. View at Publisher · View at Google Scholar
  175. Y. Bordon, “Mucosal immunology: inflammasomes induce sepsis following community breakdown,” Nature Reviews Immunology, vol. 12, pp. 400–401, 2012.
  176. E. Bezirtzoglou and E. Stavropoulou, “Immunology and probiotic impact of the newborn and young children intestinal microflora,” Anaerobe, vol. 17, pp. 369–374, 2011. View at Publisher · View at Google Scholar
  177. M. A. Hylander, D. M. Strobino, and R. Dhanireddy, “Human milk feedings and infection among very low birth weight infants,” Pediatrics, vol. 102, no. 3, p. E38, 1998. View at Scopus
  178. A. L. Morrow, G. M. Ruiz-Palacios, M. Altaye et al., “Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants,” Journal of Pediatrics, vol. 145, no. 3, pp. 297–303, 2004. View at Publisher · View at Google Scholar · View at Scopus
  179. D. S. Newburg, G. M. Ruiz-Palacios, M. Altaye et al., “Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants,” Glycobiology, vol. 14, no. 3, pp. 253–263, 2004. View at Publisher · View at Google Scholar · View at Scopus
  180. R. T. Maxson, D. D. Johnson, R. J. Jackson, and S. D. Smith, “The protective role of enteral IgA supplementation in neonatal gut-origin sepsis,” Annals of the New York Academy of Sciences, vol. 778, pp. 405–407, 1996. View at Publisher · View at Google Scholar · View at Scopus
  181. E. C. Dickinson, J. C. Gorga, M. Garrett et al., “Immunoglobulin A supplementation abrogates bacterial translocation and preserves the architecture of the intestinal epithelium,” Surgery, vol. 124, no. 2, pp. 284–290, 1998. View at Publisher · View at Google Scholar · View at Scopus
  182. H. Flores-Villaseñor, A. Canizalez-Román, J. Velazquez-Roman, et al., “Protective effects of lactoferrin chimera and bovine lactoferrin in a mouse model of enterohaemorrhagic Escherichia coli O157:H7 infection,” Biochemistry and Cell Biology, vol. 90, pp. 405–411, 2012. View at Publisher · View at Google Scholar
  183. T. J. Ochoa and T. G. Cleary, “Effect of lactoferrin on enteric pathogens,” Biochimie, vol. 91, no. 1, pp. 30–34, 2009. View at Publisher · View at Google Scholar · View at Scopus
  184. M. P. Venkatesh, D. Pham, L. Kong, and L. E. Weisman, “Prophylaxis with lactoferrin, a novel antimicrobial agent, in a neonatal rat model of coinfection,” Advances in Therapy, vol. 24, no. 5, pp. 941–954, 2007. View at Publisher · View at Google Scholar · View at Scopus
  185. M. Pammi and S. A. Abrams, “Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants,” Cochrane Database of Systematic Reviews, no. 5, Article ID CD007137, 2011. View at Publisher · View at Google Scholar
  186. V. Bhandari, M. J. Bizzarro, A. Shetty et al., “Familial and genetic susceptibility to major neonatal morbidities in preterm twins,” Pediatrics, vol. 117, no. 6, pp. 1901–1906, 2006. View at Publisher · View at Google Scholar · View at Scopus
  187. J. Arcaroli, M. B. Fessler, and E. Abraham, “Genetic polymorphisms and sepsis,” Shock, vol. 24, no. 4, pp. 300–312, 2005. View at Publisher · View at Google Scholar · View at Scopus
  188. A. Abu-Maziad, K. Schaa, E. F. Bell et al., “Role of polymorphic variants as genetic modulators of infection in neonatal sepsis,” Pediatric Research, vol. 68, no. 4, pp. 323–329, 2010. View at Publisher · View at Google Scholar · View at Scopus
  189. H. Özkan, N. Köksal, M. Çetinkaya, et al., “Serum mannose-binding lectin (MBL) gene polymorphism and low MBL levels are associated with neonatal sepsis and pneumonia,” Journal of Perinatology, vol. 32, pp. 210–217, 2012. View at Publisher · View at Google Scholar
  190. P. Ahrens, E. Kattner, B. Köhler et al., “Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants,” Pediatric Research, vol. 55, no. 4, pp. 652–656, 2004. View at Publisher · View at Google Scholar · View at Scopus