Antibiotics, pediatric dysbiosis, and disease

Cell Host and Microbe

Volumn 17, Issue 5, 2015, Pages 553-564

  Vangay, Pajau ^a   Ward, Tonya ^a   Gerber, Jeffrey S ^b   Knights, Dan ^a,c  

^a UNIVERSITY OF MINNESOTA   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^c University of Minnesota   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT;

AGING; ALLERGY; ATOPIC DERMATITIS; AUTOIMMUNE DISEASE; CHILD; CHILD DEVELOPMENT; CHILDHOOD DISEASE; CONCEPTUAL FRAMEWORK; DISEASE ASSOCIATION; DISEASE COURSE; DRUG ABUSE; DRUG USE; DYSBIOSIS; EARLY DIAGNOSIS; EPIDEMIOLOGICAL DATA; EVIDENCE BASED PRACTICE; HOST SUSCEPTIBILITY; HUMAN; IMMUNE SYSTEM; INFECTION COMPLICATION; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; METABOLIC CAPACITY; MICROBIAL COMMUNITY; MICROBIAL DIVERSITY; MOLECULAR INTERACTION; OBESITY; PATHOGENESIS; PATIENT RISK; PHENOTYPIC VARIATION; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; RISK FACTOR; TAXONOMIC RANK; CHEMICALLY INDUCED; DISEASES; DRUG EFFECTS; INFANT; MICROFLORA;

ANTI-BACTERIAL AGENTS; CHILD; DISEASE; DYSBIOSIS; HUMANS; INFANT; MICROBIOTA;

EID: 84929300450     PISSN: 19313128     EISSN: 19346069     Source Type: Journal    
DOI: 10.1016/j.chom.2015.04.006     Document Type: Review

References (134)

1. K. Aagaard, J. Ma, K.M. Antony, R. Ganu, J. Petrosino, and J. Versalovic The placenta harbors a unique microbiome Sci. Transl. Med. 6 2014 10.1126/scitranslmed.3008599
2. T.R. Abrahamsson, H.E. Jakobsson, A.F. Andersson, B. Björkstén, L. Engstrand, and M.C. Jenmalm Low diversity of the gut microbiota in infants with atopic eczema J. Allergy Clin. Immunol. 129 2012 434 440
3. M.C. Abt, L.C. Osborne, L.A. Monticelli, T.A. Doering, T. Alenghat, G.F. Sonnenberg, M.A. Paley, M. Antenus, K.L. Williams, and J. Erikson Commensal bacteria calibrate the activation threshold of innate antiviral immunity Immunity 37 2012 158 170
4. R.J. Adams, S.P. Heazlewood, K.S. Gilshenan, M. O'Brien, M.A. McGuckin, and T.H.J. Florin IgG antibodies against common gut bacteria are more diagnostic for Crohn's disease than IgG against mannan or flagellin Am. J. Gastroenterol. 103 2008 386 396
5. B. Adkins, C. Leclerc, and S. Marshall-Clarke Neonatal adaptive immunity comes of age Nat. Rev. Immunol. 4 2004 553 564
6. T.A. Ajslev, C.S. Andersen, M. Gamborg, T.I.A. Sørensen, and T. Jess Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics Int J Obes (Lond) 35 2011 522 529
7. V.N. Alexander, V. Northrup, and M.J. Bizzarro Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis J. Pediatr. 159 2011 392 397
8. R.R. Arnold, M. Brewer, and J.J. Gauthier Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms Infect. Immun. 28 1980 893 898
9. I.C. Arnold, N. Dehzad, S. Reuter, H. Martin, B. Becher, C. Taube, and A. Müller Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells J. Clin. Invest. 121 2011 3088 3093
10. T. Asahara, K. Nomoto, K. Shimizu, M. Watanuki, and R. Tanaka Increased resistance of mice to Salmonella enterica serovar Typhimurium infection by synbiotic administration of Bifidobacteria and transgalactosylated oligosaccharides J. Appl. Microbiol. 91 2001 985 996
11. K. Atarashi, J. Nishimura, T. Shima, Y. Umesaki, M. Yamamoto, M. Onoue, H. Yagita, N. Ishii, R. Evans, K. Honda, and K. Takeda ATP drives lamina propria T(H)17 cell differentiation Nature 455 2008 808 812
12. K. Atarashi, T. Tanoue, K. Oshima, W. Suda, Y. Nagano, H. Nishikawa, S. Fukuda, T. Saito, S. Narushima, and K. Hase Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota Nature 500 2013 232 236
13. S.J. Aujla, P.J. Dubin, and J.K. Kolls Th17 cells and mucosal host defense Semin. Immunol. 19 2007 377 382
14. G.B. Avery, J.G. Randolph, and T. Weaver Gastric acidity in the first day of life Pediatrics 37 1966 1005 1007
15. J.S. Ayres, N.J. Trinidad, and R.E. Vance Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota Nat. Med. 18 2012 799 806
16. J.F. Bach The effect of infections on susceptibility to autoimmune and allergic diseases N. Engl. J. Med. 347 2002 911 920
17. F. Bäckhed, J. Roswall, Y. Peng, Q. Feng, H. Jia, P. Kovatcheva-Datchary, Y. Li, Y. Xia, H. Xie, and H. Zhong Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life Cell Host Microbe 17 2015 690 703 this issue
18. L.C. Bailey, C.B. Forrest, P. Zhang, T.M. Richards, A. Livshits, and P.A. DeRusso Association of antibiotics in infancy with early childhood obesity JAMA Pediatr. 168 2014 1063 1069
19. E. Bezirtzoglou The intestinal microflora during the first weeks of life Anaerobe 3 1997 173 177
20. G. Biasucci, M. Rubini, S. Riboni, L. Morelli, E. Bessi, and C. Retetangos Mode of delivery affects the bacterial community in the newborn gut Early Hum. Dev. 86 2010 13 15
21. L. Biedermann, and G. Rogler The intestinal microbiota: its role in health and disease Eur. J. Pediatr. 174 2015 151 167
22. H. Bisgaard, N. Li, K. Bonnelykke, B.L.K. Chawes, T. Skov, G. Paludan-Müller, J. Stokholm, B. Smith, and K.A. Krogfelt Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age J. Allergy Clin. Immunol. 128 2011 646 652
23. B. Björkstén, E. Sepp, K. Julge, T. Voor, and M. Mikelsaar Allergy development and the intestinal microflora during the first year of life J. Allergy Clin. Immunol. 108 2001 516 520
24. L. Bode Human milk oligosaccharides: every baby needs a sugar mama Glycobiology 22 2012 1147 1162
25. K. Brandl, G. Plitas, C.N. Mihu, C. Ubeda, T. Jia, M. Fleisher, B. Schnabl, R.P. DeMatteo, and E.G. Pamer Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits Nature 455 2008 804 807
26. S. Brugman, F.A. Klatter, J.T.J. Visser, A.C.M. Wildeboer-Veloo, H.J.M. Harmsen, J. Rozing, and N.A. Bos Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes? Diabetologia 49 2006 2105 2108
27. C.G. Buffie, I. Jarchum, M. Equinda, L. Lipuma, A. Gobourne, A. Viale, C. Ubeda, J. Xavier, and E.G. Pamer Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis Infect. Immun. 80 2012 62 73
28. R. Cabrera-Rubio, M.C. Collado, K. Laitinen, S. Salminen, E. Isolauri, and A. Mira The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery Am. J. Clin. Nutr. 96 2012 544 551
29. P.D. Cani, R. Bibiloni, C. Knauf, A. Waget, A.M. Neyrinck, N.M. Delzenne, and R. Burcelin Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice Diabetes 57 2008 1470 1481
30. J.G. Caporaso, C.L. Lauber, E.K. Costello, D. Berg-Lyons, A. Gonzalez, J. Stombaugh, D. Knights, P. Gajer, J. Ravel, and N. Fierer Moving pictures of the human microbiome Genome Biol. 12 2011 R50
31. G. Chai, L. Governale, A.W. McMahon, J.P. Trinidad, J. Staffa, and D. Murphy Trends of outpatient prescription drug utilization in US children, 2002-2010 Pediatrics 130 2012 23 31
32. M. Cherrier, and G. Eberl The development of LTi cells Curr. Opin. Immunol. 24 2012 178 183
33. I. Cho, S. Yamanishi, L. Cox, B.A. Methé, J. Zavadil, K. Li, Z. Gao, D. Mahana, K. Raju, and I. Teitler Antibiotics in early life alter the murine colonic microbiome and adiposity Nature 488 2012 621 626
34. C.M. Cotten, S. Taylor, B. Stoll, R.N. Goldberg, N.I. Hansen, P.J. Sánchez, N. Ambalavanan, D.K. Benjamin Jr. NICHD Neonatal Research Network Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants Pediatrics 123 2009 58 66
35. L.M. Cox, S. Yamanishi, J. Sohn, A.V. Alekseyenko, J.M. Leung, I. Cho, S.G. Kim, H. Li, Z. Gao, and D. Mahana Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences Cell 158 2014 705 721
36. A. Croswell, E. Amir, P. Teggatz, M. Barman, and N.H. Salzman Prolonged impact of antibiotics on intestinal microbial ecology and susceptibility to enteric Salmonella infection Infect. Immun. 77 2009 2741 2753
37. A.G. Cummins, and F.M. Thompson Effect of breast milk and weaning on epithelial growth of the small intestine in humans Gut 51 2002 748 754
38. H.S. Deshmukh, Y. Liu, O.R. Menkiti, J. Mei, N. Dai, C.E. O'Leary, P.M. Oliver, J.K. Kolls, J.N. Weiser, and G.S. Worthen The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice Nat. Med. 20 2014 524 530
39. L. Dethlefsen, and D.A. Relman Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation Proc. Natl. Acad. Sci. USA 108 Suppl 1 2011 4554 4561
40. L. Dethlefsen, S. Huse, M.L. Sogin, and D.A. Relman The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing PLoS Biol. 6 2008 e280
41. M.G. Dominguez-Bello, E.K. Costello, M. Contreras, M. Magris, G. Hidalgo, N. Fierer, and R. Knight Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns Proc. Natl. Acad. Sci. USA 107 2010 11971 11975
42. P. Dong, Y. Yang, and W.P. Wang The role of intestinal bifidobacteria on immune system development in young rats Early Hum. Dev. 86 2010 51 58
43. C.J. Donskey, T.K. Chowdhry, M.T. Hecker, C.K. Hoyen, J.A. Hanrahan, A.M. Hujer, R.A. Hutton-Thomas, C.C. Whalen, R.A. Bonomo, and L.B. Rice Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients N. Engl. J. Med. 343 2000 1925 1932
44. J.H. Droste, M.H. Wieringa, J.J. Weyler, V.J. Nelen, P.A. Vermeire, and H.P. Van Bever Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease? Clin. Exp. Allergy 30 2000 1547 1553
45. J.L. Fierro, P.A. Prasad, A.R. Localio, R.W. Grundmeier, R.C. Wasserman, T.E. Zaoutis, and J.S. Gerber Variability in the diagnosis and treatment of group a streptococcal pharyngitis by primary care pediatricians Infect. Control Hosp. Epidemiol. 35 Suppl 3 2014 S79 S85
46. M.L. Forchielli, and W.A. Walker The role of gut-associated lymphoid tissues and mucosal defence Br. J. Nutr. 93 Suppl 1 2005 S41 S48
47. F. Fouhy, C.M. Guinane, S. Hussey, R. Wall, C.A. Ryan, E.M. Dempsey, B. Murphy, R.P. Ross, G.F. Fitzgerald, C. Stanton, and P.D. Cotter High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin Antimicrob. Agents Chemother. 56 2012 5811 5820
48. K.E. Fujimura, and S.V. Lynch Microbiota in allergy and asthma and the emerging relationship with the gut microbiome Cell Host Microbe 17 2015 592 602 this issue
49. L.J. Funkhouser, and S.R. Bordenstein Mom knows best: the universality of maternal microbial transmission PLoS Biol. 11 2013 e1001631
50. J.S. Gerber, P.A. Prasad, and A.R. Localio Variation in antibiotic prescribing across a pediatric primary care network J. Ped. Infect. Dis. 2014 10.1093/jpids/piu086 Published online October 30, 2014
51. D. Gevers, S. Kugathasan, L.A. Denson, Y. Vázquez-Baeza, W. Van Treuren, B. Ren, E. Schwager, D. Knights, S.J. Song, and M. Yassour The treatment-naive microbiome in new-onset Crohn's disease Cell Host Microbe 15 2014 382 392
52. A. Giongo, K.A. Gano, D.B. Crabb, N. Mukherjee, L.L. Novelo, G. Casella, J.C. Drew, J. Ilonen, M. Knip, and H. Hyöty Toward defining the autoimmune microbiome for type 1 diabetes ISME J. 5 2011 82 91
53. R. Gonzales, D.C. Malone, J.H. Maselli, and M.A. Sande Excessive antibiotic use for acute respiratory infections in the United States Clin. Infect. Dis. 33 2001 757 762
54. H. Goossens, M. Ferech, R. Vander Stichele, M. Elseviers ESAC Project Group Outpatient antibiotic use in Europe and association with resistance: a cross-national database study Lancet 365 2005 579 587
55. H. Haas, F.H. Falcone, M.J. Holland, G. Schramm, K. Haisch, B.F. Gibbs, A. Bufe, and M. Schlaak Early interleukin-4: its role in the switch towards a Th2 response and IgE-mediated allergy Int. Arch. Allergy Immunol. 119 1999 86 94
56. C.H.F. Hansen, D.S. Nielsen, M. Kverka, Z. Zakostelska, K. Klimesova, T. Hudcovic, H. Tlaskalova-Hogenova, and A.K. Hansen Patterns of early gut colonization shape future immune responses of the host PLoS ONE 7 2012 e34043
57. A.L. Hersh, M.A. Jackson, L.A. Hicks American Academy of Pediatrics Committee on Infectious Diseases Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics Pediatrics 132 2013 1146 1154
58. C.M. Hibberd, O.G. Brooke, N.D. Carter, M. Haug, and G. Harzer Variation in the composition of breast milk during the first 5 weeks of lactation: implications for the feeding of preterm infants Arch. Dis. Child. 57 1982 658 662
59. L.A. Hicks, T.H. Taylor Jr., and R.J. Hunkler U.S. outpatient antibiotic prescribing, 2010 N. Engl. J. Med. 368 2013 1461 1462
60. D.A. Hill, M.C. Siracusa, M.C. Abt, B.S. Kim, D. Kobuley, M. Kubo, T. Kambayashi, D.F. Larosa, E.D. Renner, and J.S. Orange Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation Nat. Med. 18 2012 538 546
61. Horton, D.B., Scott, F.I., Haynes, K., Putt, M.E., Rose, C.D., Lewis, J.D., and Strom, B.L. (2014). Antibiotic exposure and the development of juvenile idiopathic arthritis: a population-based case-control study. 66(11), Suppl. Abstract 929.
62. Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome Nature 486 2012 207 214
63. K.M. Hunt, J.A. Foster, L.J. Forney, U.M.E. Schütte, D.L. Beck, Z. Abdo, L.K. Fox, J.E. Williams, M.K. McGuire, and M.A. McGuire Characterization of the diversity and temporal stability of bacterial communities in human milk PLoS ONE 6 2011 e21313
64. I.I. Ivanov, K. Atarashi, N. Manel, E.L. Brodie, T. Shima, U. Karaoz, D. Wei, K.C. Goldfarb, C.A. Santee, and S.V. Lynch Induction of intestinal Th17 cells by segmented filamentous bacteria Cell 139 2009 485 498
65. C.C. Johnson, D.R. Ownby, S.H. Alford, S.L. Havstad, L.K. Williams, E.M. Zoratti, E.L. Peterson, and C.L.M. Joseph Antibiotic exposure in early infancy and risk for childhood atopy J. Allergy Clin. Immunol. 115 2005 1218 1224
66. C.Y. Kao, Y. Chen, P. Thai, S. Wachi, F. Huang, C. Kim, R.W. Harper, and R. Wu IL-17 markedly up-regulates β-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways J. Immunol. 173 2004 3482 3491
67. D. Knights, L.W. Parfrey, J. Zaneveld, C. Lozupone, and R. Knight Human-associated microbial signatures: examining their predictive value Cell Host Microbe 10 2011 292 296
68. J.E. Koenig, A. Spor, N. Scalfone, A.D. Fricker, J. Stombaugh, R. Knight, L.T. Angenent, and R.E. Ley Succession of microbial consortia in the developing infant gut microbiome Proc. Natl. Acad. Sci. USA 108 Suppl 1 2011 4578 4585
69. M.P. Kronman, C. Zhou, and R. Mangione-Smith Bacterial prevalence and antimicrobial prescribing trends for acute respiratory tract infections Pediatrics 134 2014 e956 e965
70. W. Landau Human colostral whey M-1 glycoproteins and their L. bifidus var. Penn. growth promoting activities Life Sci. 14 1974 967 976
71. A. Lanzavecchia, and F. Sallusto Regulation of T cell immunity by dendritic cells Cell 106 2001 263 266
72. T.D. Lawley, D.M. Bouley, Y.E. Hoy, C. Gerke, D.A. Relman, and D.M. Monack Host transmission of Salmonella enterica serovar Typhimurium is controlled by virulence factors and indigenous intestinal microbiota Infect. Immun. 76 2008 403 416
73. A. Lebenthal, and E. Lebenthal The ontogeny of the small intestinal epithelium JPEN J. Parenter. Enteral Nutr. 23 Suppl 1999 S3 S6
74. Y.K. Lee, and S.K. Mazmanian Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330 2010 1768 1773
75. R.E. Ley, P.J. Turnbaugh, S. Klein, and J.I. Gordon Microbial ecology: human gut microbes associated with obesity Nature 444 2006 1022 1023
76. N.A. Louis, and P.W. Lin The Intestinal Immune Barrier Neoreviews 10 2009 e180 e190
77. A.C. Lundell, S. Johansen, I. Adlerberth, A.E. Wold, B. Hesselmar, and A. Rudin High proportion of CD5+ B cells in infants predicts development of allergic disease J. Immunol. 193 2014 510 518
78. S.E. Macatonia, N.A. Hosken, M. Litton, P. Vieira, C.S. Hsieh, J.A. Culpepper, M. Wysocka, G. Trinchieri, K.M. Murphy, and A. O'Garra Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells J. Immunol. 154 1995 5071 5079
79. A.J. Macpherson, and N.L. Harris Interactions between commensal intestinal bacteria and the immune system Nat. Rev. Immunol. 4 2004 478 485
80. A. Maheshwari, and M. Zemlin Ontogeny of the intestinal immune system Hematology Meeting Reports (formerly Haematologica Reports) 2 2009
81. V. Mai, C.M. Young, M. Ukhanova, X. Wang, Y. Sun, G. Casella, D. Theriaque, N. Li, R. Sharma, M. Hudak, and J. Neu Fecal microbiota in premature infants prior to necrotizing enterocolitis PLoS ONE 6 2011 e20647
82. K. Mårild, W. Ye, B. Lebwohl, P.H.R. Green, M.J. Blaser, T. Card, and J.F. Ludvigsson Antibiotic exposure and the development of coeliac disease: a nationwide case-control study BMC Gastroenterol. 13 2013 109
83. S. Matamoros, C. Gras-Leguen, F. Le Vacon, G. Potel, and M.F. de La Cochetiere Development of intestinal microbiota in infants and its impact on health Trends Microbiol. 21 2013 167 173
84. C.L. Maynard, C.O. Elson, R.D. Hatton, and C.T. Weaver Reciprocal interactions of the intestinal microbiota and immune system Nature 489 2012 231 241
85. S.K. Mazmanian, J.L. Round, and D.L. Kasper A microbial symbiosis factor prevents intestinal inflammatory disease Nature 453 2008 620 625
86. L.F. McCaig, R.E. Besser, and J.M. Hughes Antimicrobial drug prescription in ambulatory care settings, United States, 1992-2000 Emerg. Infect. Dis. 9 2003 432 437
87. T.M. McKeever, S.A. Lewis, C. Smith, J. Collins, H. Heatlie, M. Frischer, and R. Hubbard Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database J. Allergy Clin. Immunol. 109 2002 43 50
88. D. Ménard Functional development of the human gastrointestinal tract: hormone- and growth factor-mediated regulatory mechanisms Can. J. Gastroenterol. 18 2004 39 44
89. L. Moles, S. Manzano, L. Fernández, A. Montilla, N. Corzo, S. Ares, J.M. Rodríguez, and I. Espinosa-Martos Bacteriological, biochemical, and immunological properties of colostrum and mature milk from mothers of extremely preterm infants J. Pediatr. Gastroenterol. Nutr. 60 2015 120 126
90. R.K. Montgomery, A.E. Mulberg, and R.J. Grand Development of the human gastrointestinal tract: twenty years of progress Gastroenterology 116 1999 702 731
91. D.R. Nash, J. Harman, E.R. Wald, and K.J. Kelleher Antibiotic prescribing by primary care physicians for children with upper respiratory tract infections Arch. Pediatr. Adolesc. Med. 156 2002 1114 1119
92. M.C. Noverr, R.M. Noggle, G.B. Toews, and G.B. Huffnagle Role of antibiotics and fungal microbiota in driving pulmonary allergic responses Infect. Immun. 72 2004 4996 5003
93. A.C. Nyquist, R. Gonzales, J.F. Steiner, and M.A. Sande Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis JAMA 279 1998 875 877
94. T. Olszak, D. An, S. Zeissig, M.P. Vera, J. Richter, A. Franke, J.N. Glickman, R. Siebert, R.M. Baron, D.L. Kasper, and R.S. Blumberg Microbial exposure during early life has persistent effects on natural killer T cell function Science 336 2012 489 493
95. M.S. Ong, D.T. Umetsu, and K.D. Mandl Consequences of antibiotics and infections in infancy: bugs, drugs, and wheezing Ann. Allergy Asthma Immunol. 112 2014 441 445
96. R.T. Paine, M.J. Tegner, and E.A. Johnson Compounded Perturbations Yield Ecological Surprises Ecosystems 1 1998 535 545
97. C. Palmer, E.M. Bik, D.B. DiGiulio, D.A. Relman, and P.O. Brown Development of the human infant intestinal microbiota PLoS Biol. 5 2007 e177
98. J. Penders, C. Thijs, C. Vink, F.F. Stelma, B. Snijders, I. Kummeling, P.A. van den Brandt, and E.E. Stobberingh Factors influencing the composition of the intestinal microbiota in early infancy Pediatrics 118 2006 511 521
99. J. Penders, K. Gerhold, E.E. Stobberingh, C. Thijs, K. Zimmermann, S. Lau, and E. Hamelmann Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood J. Allergy Clin. Immunol. 132 2013 601 607
100. S.L. Prescott, C. Macaubas, T. Smallacombe, B.J. Holt, P.D. Sly, and P.G. Holt Development of allergen-specific T-cell memory in atopic and normal children Lancet 353 1999 196 200
101. S. Rautava, O. Ruuskanen, A. Ouwehand, S. Salminen, and E. Isolauri The hygiene hypothesis of atopic disease - an extended version J. Pediatr. Gastroenterol. Nutr. 38 2004 378 388
102. V.K. Ridaura, J.J. Faith, F.E. Rey, J. Cheng, A.E. Duncan, A.L. Kau, N.W. Griffin, V. Lombard, B. Henrissat, and J.R. Bain Gut microbiota from twins discordant for obesity modulate metabolism in mice Science 341 2013 1241214
103. C.J. Robinson, and V.B. Young Antibiotic administration alters the community structure of the gastrointestinal micobiota Gut Microbes 1 2010 279 284
104. E.W. Rogier, A.L. Frantz, M.E.C. Bruno, L. Wedlund, D.A. Cohen, A.J. Stromberg, and C.S. Kaetzel Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression Proc. Natl. Acad. Sci. USA 111 2014 3074 3079
105. J.L. Round, and S.K. Mazmanian The gut microbiota shapes intestinal immune responses during health and disease Nat. Rev. Immunol. 9 2009 313 323
106. M. Rumbo, and E.J. Schiffrin Ontogeny of intestinal epithelium immune functions: developmental and environmental regulation Cell. Mol. Life Sci. 62 2005 1288 1296
107. S.L. Russell, M.J. Gold, M. Hartmann, B.P. Willing, L. Thorson, M. Wlodarska, N. Gill, M.R. Blanchet, W.W. Mohn, K.M. McNagny, and B.B. Finlay Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma EMBO Rep. 13 2012 440 447
108. S. Rutz, C. Eidenschenk, and W. Ouyang IL-22, not simply a Th17 cytokine Immunol. Rev. 252 2013 116 132
109. R. Sabat, W. Ouyang, and K. Wolk Therapeutic opportunities of the IL-22-IL-22R1 system Nat. Rev. Drug Discov. 13 2014 21 38
110. S.L. Sanos, V.L. Bui, A. Mortha, K. Oberle, C. Heners, C. Johner, and A. Diefenbach RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells Nat. Immunol. 10 2009 83 91
111. S. Sawa, M. Cherrier, M. Lochner, N. Satoh-Takayama, H.J. Fehling, F. Langa, J.P. Di Santo, and G. Eberl Lineage relationship analysis of RORgammat+ innate lymphoid cells Science 330 2010 665 669
112. I. Sekirov, N.M. Tam, M. Jogova, M.L. Robertson, Y. Li, C. Lupp, and B.B. Finlay Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection Infect. Immun. 76 2008 4726 4736
113. D.A. Sela, J. Chapman, A. Adeuya, J.H. Kim, F. Chen, T.R. Whitehead, A. Lapidus, D.S. Rokhsar, C.B. Lebrilla, and J.B. German The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome Proc. Natl. Acad. Sci. USA 105 2008 18964 18969
114. M. Sellitto, G. Bai, G. Serena, W.F. Fricke, C. Sturgeon, P. Gajer, J.R. White, S.S.K. Koenig, J. Sakamoto, and D. Boothe Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants PLoS ONE 7 2012 e33387
115. N. Shehab, P.R. Patel, A. Srinivasan, and D.S. Budnitz Emergency department visits for antibiotic-associated adverse events Clin. Infect. Dis. 47 2008 735 743
116. Q. Shu, H. Lin, K.J. Rutherfurd, S.G. Fenwick, J. Prasad, P.K. Gopal, and H.S. Gill Dietary Bifidobacterium lactis (HN019) enhances resistance to oral Salmonella typhimurium infection in mice Microbiol. Immunol. 44 2000 213 222
117. Y.M. Sjögren, M.C. Jenmalm, M.F. Böttcher, B. Björkstén, and E. Sverremark-Ekström Altered early infant gut microbiota in children developing allergy up to 5 years of age Clin. Exp. Allergy 39 2009 518 526
118. G.F. Sonnenberg, L.A. Monticelli, T. Alenghat, T.C. Fung, N.A. Hutnick, J. Kunisawa, N. Shibata, S. Grunberg, R. Sinha, and A.M. Zahm Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria Science 336 2012 1321 1325
119. A.T. Stefka, T. Feehley, P. Tripathi, J. Qiu, K. McCoy, S.K. Mazmanian, M.Y. Tjota, G.Y. Seo, S. Cao, and B.R. Theriault Commensal bacteria protect against food allergen sensitization Proc. Natl. Acad. Sci. USA 111 2014 13145 13150
120. S. Subramanian, S. Huq, T. Yatsunenko, R. Haque, M. Mahfuz, M.A. Alam, A. Benezra, J. DeStefano, M.F. Meier, and B.D. Muegge Persistent gut microbiota immaturity in malnourished Bangladeshi children Nature 510 2014 417 421
121. S. Tanaka, T. Kobayashi, P. Songjinda, A. Tateyama, M. Tsubouchi, C. Kiyohara, T. Shirakawa, K. Sonomoto, and J. Nakayama Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota FEMS Immunol. Med. Microbiol. 56 2009 80 87
122. S.M. Teo, D. Mok, K. Pham, M. Kusel, M. Serralha, N. Troy, B.J. Holt, B.J. Hales, M.L. Walker, and E. Hollams The infant nasopharyngeal microbiome impacts the incidence of lower respiratory infection and risk of asthma development Cell Host Microbe 2015 10.1016/j.chom.2015.03.008 Published online April 8, 2015
123. N. Tormo-Badia, Å. Håkansson, K. Vasudevan, G. Molin, S. Ahrné, and C.M. Cilio Antibiotic treatment of pregnant non-obese diabetic mice leads to altered gut microbiota and intestinal immunological changes in the offspring Scand. J. Immunol. 80 2014 250 260
124. L. Trasande, J. Blustein, M. Liu, E. Corwin, L.M. Cox, and M.J. Blaser Infant antibiotic exposures and early-life body mass Int J Obes (Lond) 37 2013 16 23
125. N.M. Tsuji, and A. Kosaka Oral tolerance: intestinal homeostasis and antigen-specific regulatory T cells Trends Immunol. 29 2008 532 540
126. P.J. Turnbaugh, R.E. Ley, M.A. Mahowald, V. Magrini, E.R. Mardis, and J.I. Gordon An obesity-associated gut microbiome with increased capacity for energy harvest Nature 444 2006 1027 1031
127. P.J. Turnbaugh, M. Hamady, T. Yatsunenko, B.L. Cantarel, A. Duncan, R.E. Ley, M.L. Sogin, W.J. Jones, B.A. Roe, and J.P. Affourtit A core gut microbiome in obese and lean twins Nature 457 2009 480 484
128. P.A. Vaishampayan, J.V. Kuehl, J.L. Froula, J.L. Morgan, H. Ochman, and M.P. Francino Comparative metagenomics and population dynamics of the gut microbiota in mother and infant Genome Biol. Evol. 2 2010 53 66
129. V.H. van der Velden, M.P. Laan, M.R. Baert, R. de Waal Malefyt, H.J. Neijens, and H.F. Savelkoul Selective development of a strong Th2 cytokine profile in high-risk children who develop atopy: risk factors and regulatory role of IFN-gamma, IL-4 and IL-10 Clin. Exp. Allergy 31 2001 997 1006
130. Y. Wang, J.D. Hoenig, K.J. Malin, S. Qamar, E.O. Petrof, J. Sun, D.A. Antonopoulos, E.B. Chang, and E.C. Claud 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis ISME J. 3 2009 944 954
131. L. Wen, R.E. Ley, P.Y. Volchkov, P.B. Stranges, L. Avanesyan, A.C. Stonebraker, C. Hu, F.S. Wong, G.L. Szot, and J.A. Bluestone Innate immunity and intestinal microbiota in the development of Type 1 diabetes Nature 455 2008 1109 1113
132. H.J. Wu, I.I. Ivanov, J. Darce, K. Hattori, T. Shima, Y. Umesaki, D.R. Littman, C. Benoist, and D. Mathis Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells Immunity 32 2010 815 827
133. T. Yatsunenko, F.E. Rey, M.J. Manary, I. Trehan, M.G. Dominguez-Bello, M. Contreras, M. Magris, G. Hidalgo, R.N. Baldassano, and A.P. Anokhin Human gut microbiome viewed across age and geography Nature 486 2012 222 227
134. L. Yurkovetskiy, J.M. Pickard, and A.V. Chervonsky Microbiota and Autoimmunity: Venues Less Visited Cell Host Microbe 17 2015 548 552 this issue