The Journal of Pediatrics
Volume 149, Issue 5, Supplement , Pages S107-S114 , November 2006

Bacterial colonization, probiotics, and clinical disease

Presented as part of a symposium recognizing the 25th anniversary of the Bristol-Myers Squibb “Freedom to Discover” Nutrition Grants Program, University of Cincinnati, Cincinnati, OH, June 7-8, 2005.

  • Meiqian Weng, MD, PhD
  • ,
  • W. Allan Walker, MD

      Affiliations

    • Corresponding Author InformationReprint requests: W. Allan Walker, MD, Development Gastroenterology Laboratory, Pediatric Gastroenterology and Nutrition Unit, Massachusetts General Hospital for Children, Harvard Medical School, 114 16th Street (114-3405), Charlestown, MA 02129.

Received 14 April 2006 ,Accepted 1 June 2006.

References 

  1. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002;347:911–920
  2. Aberg N, Hesselmar B, Aberg B, Eriksson B. Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991. Clin Exp Allergy. 1995;25:815–819
  3. Holt PG, Macaubas C. Development of long-term tolerance versus sensitization to environmental allergens during the perinatal period. Curr Opin Immunol. 1997;9:782–787
  4. Stene LC, Nafstad P. Relation between occurrence of type 1 diabetes and asthma. Lancet. 2001;357:607–608
  5. Yazdanbakhsh M, Kremsner PG, Ree RV. Allergy, parasites, and the hygiene hypothesis. Science. 2002;296:490–494
  6. Romagnani S. The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?. Immunology. 2004;112:352–363
  7. Holt PG. Parasites, atopy, and the hygiene hypothesis: resolution of a paradox?. Lancet. 2000;356:1699–1701
  8. Shi HN, Walker A. Bacterial colonization and the development of intestinal defences. Can J Gastroenterol. 2004;18:493–500
  9. Macpherson AJ, Uhr T. Compartmentalization of the mucosal immune response to commensal intestinal bacteria. Ann N Y Acad Sci. 2004;1029:36–43
  10. Yamanaka T, Helgeland L, Farstad IN, Fukushinma H, Midtvedt T, Braandtzaeg P. Microbial colonization drives lymphocyte accumulation and differentiation in the follicle-associated epithelium of Peyer’s patches. J Immunol. 2003;170:816–822
  11. Schofield DA, Westwater C, Balish E. Beta-defensin expression in immunocompetent and immunodeficient germ-free and Candida albicans-monoassociated mice. J Infect Dis. 2004;190:1327–1334
  12. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JL. Molecular analysis of commensal host–microbial relationships in the intestine. Science. 2001;291:881–884
  13. Umesaki Y, Setoyama H. Structure of the intestinal flora responsible for development of the gut immune system in a rodent model. Microbes Infect. 2000;2:1343–1351
  14. Macpherson AJ, Uhr T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004;303:1624–1625
  15. Ibnou-Zekri N, Blum S, Schiffrin EJ, Von der Weid T. Divergent patterns of colonization and immune response elicited from two intestinal lactobacillus strains that display similar properties in vitro. Infect Immunol. 2003;71:428–436
  16. Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL. Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol. 2004;172:1118–1124
  17. Prioult G, Fliss I, Pecquet S. Effect of probiotic bacteria on induction and maintenance of oral tolerance to β-lactoglobulin in gnotobiotic mice. Clin Diagn Lab Immunol. 2003;10:787–792
  18. He F, Ouwehand AC, Isolauri E, Hashimoto H, Benno Y, Salminen S. Comparison of mucosal adhesion and species identification of bifidobacteria isolated from healthy and allergic infants. FEMS Immunol Med Microbiol. 2001;30:43–47
  19. Linskens RK, Huijsdens XW, Savelkoul PHM, Vandenbroucke-Grauls CMJE, Meuwissen SGM. The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. Scand J Gastroenterol. 2001;(234):29–40
  20. Friman V, Nowrouzian F, Adlerberth I, Wold AE. Increased frequency of intestinal Escherichia coli–carrying genes for S fimbriae and haemolysin in IgA-deficient individuals. Microb Pathog. 2002;32:35–42
  21. Aim JS, Swartz J, Bjorksten B, Engstrand L, Engstrom J, Kuhn I, et al. An anthroposophic lifestyle and intestinal microflora in infancy. Pediatr Allergy Immunol. 2002;13:402–411
  22. Samuelsson U, Ludvigsson J. The concentrations of short-chain fatty acids and other microflora-associated characteristics in faeces from children with newly diagnosed type 1 diabetes and control children and their family members. Diabetes Med. 2004;21:64–67
  23. Walker A. Role of nutrients and bacterial colonization in the development of intestinal host defense. J Pediatr Gastroenterol Nutr. 2000;30(Suppl 2):S2–S7
  24. Bourlioux P, Koletzko B, Guarner F, Braesco V. The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium on “The Intelligent Intestine,” Paris, June 14, 2002. Am J Clin Nutr. 2003;78:675–683
  25. Field CJ. The immunological components of human milk and their effect on immune development in infants. J Nutr. 2005;135:1–4
  26. Hanson LA, Korotkova M, Telemo E. Breast-feeding, infant formulas, and the immune system. Ann Allegy Asthma Immunol. 2003;90(Suppl 3):59–63
  27. Neikkilä MP, Saris PEJ. Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. J Appl Microbiol. 2003;95:471–478
  28. Bomba A, Nemcova R, Gancarcikova S, Herich R, Pistl J, Revajova V, et al. The influence of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on lactobacilli adhesion to the intestinal mucosa and on immunity in gnotobiotic piglets. Berl Munch Tierarztl Wochenschr. 2003;116:312–316
  29. Bry L, Falk PG, Midtvedt T, Gordon JI. A model of host-microbial interactions in an open mammalian ecosystem. Science. 1996;273:1380–1383
  30. Coyne MJ, Reinap B, Lee MM, Comstock LE. Human symbionts use a host-like pathway for surface fucosylation. Science. 2005;307:1778–1781
  31. Gebbink MF, Claessen D, Bouma B, Dijkhuizen L, Wösten HA. Amyloids: a functional coat for microorganisms. Nat Rev Microbiol. 2005;3:333–341
  32. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335–376
  33. Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavel RA, et al. A toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004;303:1522–1526
  34. Underhill DM. Toll-like receptors and microbes take aim at each other. Curr Opin Immunol. 2004;16:483–487
  35. Cook DN, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease. Nat Immunol. 2004;5:975–979
  36. Abreu MT, Fukata M, Arditi M. TLR signaling in the gut in health and disease. J Immunol. 2005;174:4453–4460
  37. Kelly D, Conway S. Bacterial modulation of mucosal innate immunity. Mol Immunol. 2005;42:895–901
  38. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229–241
  39. Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med. 2004;197:403–411
  40. Vora P, Youdim A, Thomas LS, Fukata M, Tesfay SY, Lukasek K, et al. β-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J Immunol. 2004;173:5398–5405
  41. Eder W, Kimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrlander C, et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol. 2004;113:482–488
  42. Park Y, Park S, Yoo E, Kim D, Shin H. Association of the polymorphism for toll-like receptor 2 with type 1 diabetes susceptibility. Ann N Y Acad Sci. 2004;1037:170–174
  43. Franchimont D, Vermeire S, EI Housni H, Pierik M, Van Steen K, Gustot T, et al. Deficient host-bacteria interactions in inflammatory bowel disease? (The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis). Gut. 2004;53:987–992
  44. Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, et al. The Arg753Gln polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. Eur Respir J. 2004;23:219–223
  45. Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, et al. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to Legionnaires’ disease. J Exp Med. 2003;198:1563–1572
  46. Noguchi E, Nishimura F, Fukai H, Kim J, Ichikawa K, Shibasaki M, et al. An association study of asthma and total serum immunoglobin E levels for toll-like receptor polymorphisms in a Japanese population. Clin Exp Allergy. 2004;34:163–166
  47. Uehara A, Yang S, Fujimoto Y, Fukase K, Kusumoto S, Shibata K, et al. Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in human monocytic cells in culture. Cell Microbiol. 2005;7:53–61
  48. Netea MG, Ferwerda G, de Jong DJ, Jansen T, Jacobs L, Kramer M, et al. Nucleotide-binding oligomerization domain-2 modulates specific TLR pathways for the induction of cytokine release. J Immunol. 2005;174:6518–6523
  49. van Heel DA, Ghosh S, Butler M, Hunt KA, Lundberg AM, Ahmad T, et al. Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn’s disease. Lancet. 2005;365:1794–1796
  50. Buning C, Molnar T, Nagy F, Lonovics J, Weltrich R, Bochow B, et al. NOD2/CARD15 gene polymorphism in patients with inflammatory bowel disease: is Hungary different?. World J Gastroenterol. 2005;11:407–411
  51. Gazouli M, Mantzaris G, Kotsinas A, Zacharatos P, Papalambros E, Archimandritis A, et al. Association between polymorphism in the toll-like receptor 4, CD14, and CARD15/NOD2 and inflammatory bowel disease in the Greek population. World J Gastroenterol. 2005;11:681–685
  52. Zouiten-Mekki L, Zaouali H, Boubaker J, Karoui S, Fekih M, Matri S, et al. CARD15/NOD2 in a Tunisian population with Crohn’s disease. Dig Dis Sci. 2005;50:130–135
  53. Gao M, Cao Q, Luo LH, Wu ML, Hu WL, Si JM. NOD2/CARD15 gene polymorphism and susceptibility to Crohn’s disease in Chinese Han population. Zhonghua Nei Ke Za Zhi. 2005;44:210–212
  54. Idestrom M, Rubio C, Granath F, Finkel Y, Hugot JP. CARD15 mutations are rare in Swedish pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2005;40:456–460
  55. McGovern DP, Hysi P, Ahmad T, van Heel DA, Moffatt MF, Carey A, et al. Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet. 2005;14:1245–1250
  56. Otte JM, Cario E, Podolsky DK. Mechanism of cross-hyporesponsiveness to toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology. 2004;126:1054–1070
  57. Kim JG, Lee SJ, Kagnoff MF. NOD1 is an essential signal transducer in intestinal epithelial cells infected with bacteria that avoid recognition by toll-like receptors. Infect Immunol. 2004;72:1487–1495
  58. Melmed G, Thomas LS, Lee N, Tesfay SY, Lukasek K, Michelsen KS, et al. Human intestinal epithelial cells are broadly unresponsive to toll-like receptor 2–dependent bacterial ligands: implications for host-microbial interactions in the gut. J Immunol. 2003;170:1406–1415
  59. Hornef MW, Frisan T, Vandewalle A, Normark S, Richter-Dahlfors A. toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med. 2002;195:559–570
  60. Hornef MW, Normark BH, Vandewalle A, Normark S. Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in intestinal epithelial cells. J Exp Med. 2003;198:1225–1235
  61. Fukao T, Koyasu S. PI3K and negative regulation of TLR signaling. Trends Immunol. 2003;24:358–363
  62. Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, et al. SIGIRR, a negative regulator of toll-like receptor-interleukin 1 receptor signaling. Nat Immunol. 2003;4:920–927
  63. Janssens S, Burns K, Tschopp J, Beyaert R. Regulation of interleukin-1 and lipopolysaccharide-induced NF-κB activation by alternative splicing of MyD88. Curr Biol. 2002;12:467–471
  64. Kobayashi K, Hernandez LD, Galan JE. IRAK-M is a negative regulator of toll-like receptor signaling. Cell. 2002;110:191–202
  65. Yamakami M, Yokosawa H. Tom1 (target of Myb 1) is a novel negative regulator of interleukin-1- and tumor necrosis factor-induced signaling pathways. Biol Pharm Bull. 2004;27:564–566
  66. Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M, et al. SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity. 2002;17:583–591
  67. Watanabe T, Kitani A, Murray P, Strober W. NOD2 is a negative regulator of toll-like receptor 2-mediated T helper type 1 responses. Nature. 2004;5:800–808
  68. Shinohara H, Inoue A, Toyama-Sorimachi N, Nagai Y, Yasuda T, Suzuki H, et al. DOK-1 and DOK-2 are negative regulation of lipopolysaccharide-induced signaling. J Exp Med. 2005;201:333–339
  69. Chuang TH, Ulevitch R. Triad3A, an E3 ubiquitin-protein ligase regulating toll-like receptors. Nat Immunol. 2004;5:495–502
  70. Gon Y, Asai Y, Hashimoto S, Mizumura K, Jibiki I, Machino T, et al. A20 inhibits toll-like receptor 2- and 4-mediated interleukin 8 synthesis in airway epithelial cells. Am J Respir Cell Mol Biol. 2004;31:330–336
  71. Brint EK, Xu DM, Liu HY, Dunne A, Mckenzie AN, O’Neill LA, et al. ST2 is an inhibitor of interleukin 1 receptor and toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat Immunol. 2004;5:373–379
  72. Divanovic S, Trompette A, Atabani SF, Madan R, Golenbock DT, Visintin A, et al. Negative regulation of toll-like receptor 4 signaling by the toll-like receptor homolog RP105. Nat Immunol. 2005;6:571–578
  73. Hamerman JA, Tchal NK, Lowell CA, Lanier LL. Enhanced toll-like receptor responses in the absence of signaling adaptor DAP12. Nat Immunol. 2005;6:579–586
  74. Rimoldi M, Chieppa M, Vulcano M, Allavena P, Rescigno M. Intestinal epithelial cells control dendritic cell function. Ann N Y Acad Sci. 2004;1029:66–74
  75. Sansonetti P. Phagocytosis of bacterial pathogens: implications in the host response. Semin Immunol. 2001;13:381–390
  76. Shroff KE, Meslin K, Cebra JJ. Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut. Infect Immunol. 1995;63:3904–3913
  77. Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, Kagnoff MF. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol. 2005;174:4901–4907
  78. Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V, et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-α ubiquitination. Science. 2000;289:1560–1563
  79. Fort MM, Mozaffarian A, Stover AG, Correia Jda S, Johnson DA, Crane RT, et al. A synthetic TLR4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease. J Immunol. 2005;174:6416–6423
  80. Rook GA, Brunet LR. Microbes, immunoregulation, and the gut. Gut. 2005;54:317–320
  81. Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomized placebo-controlled trial. Lancet. 2003;361:1869–1871
  82. Sullivan A, Nord CE. Probiotics and gastrointestinal disease. J Intern Med. 2005;257:78–92

 Dr. Walker is a recipient of a Bristol-Myers Squibb–Mead Johnson Unrestricted Nutrition Research Grant. Mead Johnson sponsored the symposium and provided an honorarium for conference attendance, presentation of the paper, and submission of a manuscript. The authors are entirely and exclusively responsible for its content.

PII: S0022-3476(06)00622-6

doi: 10.1016/j.jpeds.2006.06.061

The Journal of Pediatrics
Volume 149, Issue 5, Supplement , Pages S107-S114 , November 2006