Maternally acquired genotoxic Escherichia coli alters offspring's intestinal homeostasis

Gut Microbes

Volumn 5, Issue 3, 2014, Pages

  Payros, Delphine ^a,b,c,d,e   Secher, Thomas ^a,b,c,d   Boury, Michèle ^a,b,c,d   Brehin, Camille ^a,b,c,d,f   Ménard, Sandrine ^e   Salvadorcartier, Christel ^e   Cuevas Ramos, Gabriel ^a,b,c,d   Watrin, Claude ^a,b,c,d   Marcq, Ingrid ^g   Nougayrède, Jean Philippe ^a,b,c,d   Dubois, Damien ^a,b,c,d,f   Bedu, Antoine ^h   Garnier, Fabien ^i,j   Clermont, Olivier ^b   Denamur, Erick ^b   Plaisancié, Pascale ^k   Theodorou, Vassilia ^e   Fioramonti, Jean ^e   Olier, Maïwenn ^a,b,c,d,e   Oswald, Eric ^a,b,c,d,f  

^a CEMAGREF   (France)

^b INSERM   (France)

^c CNRS   (France)

^d UNIVERSITÉ DE TOULOUSE   (France)

^e UNIVERSITÉ DE TOULOUSE   (France)

^f CHU PURPAN   (France)

^g UNIVERSITÉ DE PICARDIE JULES VERNE   (France)

^h LIMOGES UNIVERSITY HOSPITAL   (France)

ⁱ UMR 1092   (France)

^j UNIVERSITY OF LIMOGES   (France)

^k CarMeN   (France)

more..

Author keywords

Colibactin; Epithelial differentiation; Epithelial proliferation; Escherichia coli; Genotoxicity; Gut; Intestinal barrier; Neonate

Indexed keywords

COLIBACTIN; PEPTIDE; POLYKETIDE;

ANIMAL; ANIMAL MODEL; DNA DAMAGE; DRUG EFFECTS; ESCHERICHIA COLI; FEMALE; GASTROINTESTINAL TRACT; HUMAN; MALE; METABOLISM; MICROBIOLOGY; NEWBORN; PREGNANCY; WISTAR RAT;

ANIMALS; DNA DAMAGE; ESCHERICHIA COLI; FEMALE; GASTROINTESTINAL TRACT; HUMANS; INFANT, NEWBORN; MALE; MODELS, ANIMAL; PEPTIDES; POLYKETIDES; PREGNANCY; RATS, WISTAR;

EID: 84905157986     PISSN: 19490976     EISSN: 19490984     Source Type: Journal    
DOI: 10.4161/gmic.28932     Document Type: Article

References (82)

1. Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol 2012; 9:565-76;PMID:22890113; http://dx.doi. org/10.1038/nrgastro.2012.144
2. SommerF, BäckhedF. The gut microbiota--masters of host development and physiology. Nat Rev Microbiol 2013; 11:227-38;PMID:23435359; http://dx.doi. org/10.1038/nrmicro2974
3. Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr 2009; 98:229-38;PMID:19143664; http://dx.doi. org/10.1111/j.1651-2227.2008.01060.x
4. Costello EK, StagamanK, DethlefsenL, Bohannan BJ, Relman DA. The application of ecological theory toward an understanding of the human microbiome. Science 2012; 336:1255-62;PMID:22674335; http://dx.doi.org/10.1126/science.1224203
5. Dominguez-Bello MG, Costello EK, Contreras M, MagrisM, HidalgoG, FiererN, Knight R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 2010; 107:11971-5;PMID:20566857; http://dx.doi.org/10.1073/ pnas.1002601107
6. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, Angenent LT, Ley RE. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A 2011; 108(Suppl 1):4578-85;PMID:20668239; http://dx.doi.org/10.1073/pnas.1000081107
7. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, KummelingI, van den Brandt PA, Stobberingh EE. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006; 118:511-21;PMID:16882802; http://dx.doi.org/10.1542/ peds.2005-2824
8. Vaishampayan PA, Kuehl JV, Froula JL, Morgan JL, Ochman H, Francino MP. Comparative metagenomics and population dynamics of the gut microbiota in mother and infant. Genome Biol Evol 2010; 2:53-66;PMID:20333224; http://dx.doi. org/10.1093/gbe/evp057
9. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, et al. Human gut microbiome viewed across age and geography. Nature 2012; 486:222-7; PMID:22699611
10. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol 2007; 5:e177; PMID:17594176; http://dx.doi.org/10.1371/journal. pbio.0050177
11. Tu r nbau gh PJ, Ley RE, Mahowald MA, MagriniV, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444:1027-31;PMID:17183312; http:// dx.doi.org/10.1038/nature05414
12. Martens EC, Chiang HC, Gordon JI. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 2008; 4:447-57;PMID:18996345; http://dx.doi.org/10.1016/j.chom.2008.09.007
13. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004; 101:15718-23;PMI D:15505215; http://dx.doi. org/10.1073/pnas.0407076101
14. XuJ, Gordon JI. Honor thy symbionts. Proc Natl Acad Sci U S A 2003; 100:10452-9;PMID:12923294; http://dx.doi.org/10.1073/pnas.1734063100
15. ChungH, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, Reading NC, Villablanca EJ, Wang S, Mora JR, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell 2012; 149:1578-93;PMID:22726443; http://dx.doi. org/10.1016/j.cell.2012.04.037
16. HeczkoU, AbeA, Finlay BB. Segmented filamentous bacteria prevent colonization of enteropathogenic Escherichia coliO103 in rabbits. J Infect Dis 2000; 181:1027-33;PMID:10720527; http://dx.doi. org/10.1086/315348
17. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009; 139:485-98;PMID:19836068; http://dx.doi.org/10.1016/j. cell.2009.09.033
18. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science 2012; 336:1268-73;PMID:22674334; http://dx.doi.org/10.1126/science.1223490
19. Hooper LV, Macpherson AJ. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 2010; 10:159-69; PMID:20182457; http://dx.doi.org/10.1038/nri2710
20. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 2005; 122:107-18;PMID:16009137; http://dx.doi.org/10.1016/j.cell.2005.05.007
21. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, EdbergS, MedzhitovR. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004; 118:229-41; PMID:15260992; http://dx.doi.org/10.1016/j. cell.2004.07.002
22. Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A 2002; 99:15451-5;PMID:12432102; http://dx.doi.org/10.1073/pnas.202604299
23. Sudo N, Sawamura S, Tanaka K, Aiba Y, Kubo C, KogaY. The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J Immunol 1997; 159:1739-45;PMID:9257835
24. Park HK, Shim SS, Kim SY, Park JH, Park SE, Kim HJ, Kang BC, Kim CM. Molecular analysis of colonized bacteria in a human newborn infant gut. J Microbiol 2005; 43:345-53;PMID:16145549
25. Favier CF, Vaughan EE, De Vos WM, Akkermans AD. Molecular monitoring of succession of bacterial communities in human neonates. Appl Environ Microbiol 2002; 68:219-26;PMID:11772630; http://dx.doi.org/10.1128/AEM.68.1.219-226.2002
26. Mackie RI, Sghir A, Gaskins HR. Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 1999; 69:1035S-45S; PMID:10232646
27. Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics 1983; 72:317-21;PMID:6412205
28. Nowrouzian FL, AdlerberthI, Wold AE. Enhanced persistence in the colonic microbiota of Escherichia colistrains belonging to phylogenetic group B2: role of virulence factors and adherence to colonic cells. Microbes Infect 2006; 8:834-40;PMID:16483819; http://dx.doi.org/10.1016/j.micinf.2005.10.011
29. Tena illonO, SkurnikD, PicardB, DenamurE. The population genetics of commensal Escherichia coli. Nat Rev Microbiol 2010; 8:207-17;PMID:20157339; http://dx.doi.org/10.1038/nrmicro2298
30. Gordon DM, Clermont O, Tolle y H, Denamur E. Assigning Escherichia colistrains to phylogenetic groups: multi-locus sequence typing versus the PCR triplex method. Environ Microbiol 2008; 10:2484-96;PMID:18518895; http://dx.doi. org/10.1111/j.1462-2920.2008.01669.x
31. Smati M, Clermont O, Le Gal F, Schichmanoff O, Jauréguy F, Eddi A, Denamur E, Picard B; Coliville Group. Real-time PCR for quantitative analysis of human commensal Escherichia coli populations reveals a high frequency of subdominant phylogroups. Appl Environ Microbiol 2013; 79:5005-12;PMID:23770894; http://dx.doi.org/10.1128/ AEM.01423-13
32. Escobar-PáramoP, GrenetK, Le Menac'hA, RodeL, SalgadoE, AmorinC, GouriouS, PicardB, Rahimy MC, Andremont A, et al. Large-scale population structure of human commensal Escherichia coli isolates. Appl Environ Microbiol 2004; 70:5698-700;PMID:15345464; http://dx.doi.org/10.1128/ AEM.70.9.5698-5700.2004
33. Gordon DM, Stern SE, Collignon PJ. Influence of the age and sex of human hosts on the distribution of Escherichia coliECOR groups and virulence traits. Microbiology 2005; 151:15-23;PMID:15632421; http://dx.doi.org/10.1099/mic.0.27425-0
34. NowrouzianF, HesselmarB, SaalmanR, Strannegard IL, AbergN, Wold AE, AdlerberthI. Escherichia coli in infants' intestinal microflora: colonization rate, strain turnover, and virulence gene carriage. Pediatr Res 2003; 54:8-14;PMID:12700366; http://dx.doi. org/10.1203/01.PDR.0000069843.20655.EE
35. Nowrouzian FL, Wold AE, AdlerberthI. Escherichia colistrains belonging to phylogenetic group B2 have superior capacity to persist in the intestinal microflora of infants. J Infect Dis 2005; 191:1078-83; PMID:15747243; http://dx.doi.org/10.1086/427996
36. Nougayrède JP, Homburg S, Taieb F, Boury M, Brzuszkiewicz E, Gottschalk G, Buchrieser C, Hacker J, Dobrindt U, Oswald E. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 2006; 313:848-51;PMID:16902142; ht t p://dx. doi.org/10.1126/science.1127059
37. Nowrouzian FL, Oswald E. Escherichia colistrains with the capacity for long-term persistence in the bowel microbiota carry the potentially genotoxic pks island. Microb Pathog 2012; 53:180-2; PMID:22709536; http://dx.doi.org/10.1016/j. micpath.2012.05.011
38. Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrède JP. Escherichia coliinduces DNA damage in vivoand triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A 2010; 107:11537-42;PMID:20534522; http://dx.doi. org/10.1073/pnas.1001261107
39. SecherT, Samba-LouakaA, OswaldE, Nougayrède JP. Escherichia coliproducing colibactin triggers premature and transmissible senescence in mammalian cells. PLoS One 2013; 8:e77157; PMI D:24116215; http://dx.doi.org/10.1371/journal. pone.0 077157
40. Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 2012; 338:120-3; PMID:22903521; http://dx.doi.org/10.1126/ science.1224820
41. Le GallT, ClermontO, GouriouS, PicardB, Nassif X, DenamurE, Tena illonO. Extraintestinal virulence is a coincidental by-product of commensalism in B2 phylogenetic group Escherichia colistrains. Mol Biol Evol 2007; 24:2373-84;PMID:17709333; http:// dx.doi.org/10.1093/molbev/msm172
42. Olier M, Marcq I, Salvador-Cartier C, Secher T, DobrindtU, BouryM, BacquiéV, PénaryM, Gaultier E, Nougayrède JP, et al. Genotoxicity of Escherichia coliNissle 1917 strain cannot be dissociated from its probiotic activity. Gut Microbes 2012; 3:501-9;PMID:22895085; http://dx.doi.org/10.4161/ gmic.21737
43. Scholtens PA, OozeerR, MartinR, Amor KB, Knol J. The early settlers: intestinal microbiology in early life. Annu Rev Food Sci Technol 2012; 3:425-47;PMID:22224552; http://dx.doi.org/10.1146/ annurev-food-022811-101120
44. McClintock B. The Stability of Broken Ends of Chromosomes in Zea Mays. Genetics 1941; 26:234-82;PMID:17247004
45. FenechM, Kirsch-VoldersM, Natarajan AT, Surralles J, Crott JW, Parry J, Norppa H, Eastmond DA, Tuc ker JD, Thomas P. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 2011; 26:125-32;PMID:21164193; http://dx.doi.org/10.1093/mutage/geq052
46. Cummins AG, Jones BJ, Thompson FM. Postnatal epithelial growth of the small intestine in the rat occurs by both crypt fission and crypt hyperplasia. Dig Dis Sci 2006; 51:718-23;PMID:16614994; http://dx.doi.org/10.1007/s10620-006-3197-9
47. St Clair WH, Osborne JW. Crypt fission and crypt number in the small and large bowel of postnatal rats. Cell Tissue Kinet 1985; 18:255-62;PMID:3986870
48. Dehmer JJ, Garrison AP, Speck KE, Dekaney CM, Van Landeghem L, Sun X, Henning SJ, Helmrath MA. Expansion of intestinal epithelial stem cells during murine development. PLoS One 2011; 6:e27070;PMID:22102874; http://dx.doi. org/10.1371/journal.pone.0027070
49. Wasan HS, Park HS, Liu KC, Mandir NK, Winnett A, Sasieni P, Bodmer WF, Goodlad RA, Wright NA. APC in the regulation of intestinal crypt fission. J Pathol 1998; 185:246-55;PMID:9771477; http://dx.doi.org/10.1002/ (SICI)1096-9896(199807)185:3<246::AIDPATH90>3.0.CO;2-8
50. Preston SL, Wong WM, Chan AO, Poulsom R, JefferyR, Goodlad RA, MandirN, EliaG, Novelli M, Bodmer WF, et al. Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission. Cancer Res 2003; 63:3819-25;PMID:12839979
51. DrozdowskiL, Thomson AB. Intestinal hormones and growth factors: effects on the small intestine. World J Gastroenterol 2009; 15:385-406;PMI D:191524 42; http://dx.doi.org/10.3748/wjg.15.385
52. Dethlefsen L, Eckburg PB, Bik EM, Relman DA. Assembly of the human intestinal microbiota. Trends Ecol Evol 2006; 21:517-23;PMID:16820245; http:// dx.doi.org/10.1016/j.tree.2006.06.013
53. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al.; MetaHIT Consortium. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464:59-65;PMID:20203603; http://dx.doi.org/10.1038/ nature08821
54. Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science 2001; 292:1115-8;PMID:11352068; http://dx.doi.org/10.1126/ science.1058709
55. Faith JJ, Guruge JL, CharbonneauM, Subramanian S, Seedorf H, Goodman AL, Clemente JC, Knight R, Heath AC, Leibel RL, et al. The long-term stability of the human gut microbiota. Science 2013; 341:1237439;PMID:23828941; http://dx.doi. org/10.1126/science.1237439
56. Neu J. Perinatal and neonatal manipulation of the intestinal microbiome: a note of caution. Nutr Rev 2007; 65:282-5;PMID:17605304; http://dx.doi. org/10.1111/j.1753-4887.2007.tb00305.x
57. FanaroS, ChiericiR, GuerriniP, VigiV. Intestinal microflora in early infancy: composition and development. Acta Paediatr Suppl 2003; 91:48-55; PMID:14599042
58. Bailey JK, Pinyon JL, Anantham S, Hall RM. Commensal Escherichia coli of healthy humans: a reservoir for antibiotic-resistance determinants. J Med Microbiol 2010; 59:1331-9;PMID:20671087; http://dx.doi.org/10.1099/jmm.0.022475-0
59. BarreauF, FerrierL, FioramontiJ, BuenoL. Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats. Gut 2004; 53:501-6;PMI D:15016743; http:// dx.doi.org/10.1136/gut.2003.024174
60. Barreau F, Ferrier L, Fioramonti J, Bueno L. New insights in the etiology and pathophysiology of irritable bowel syndrome: contribution of neonatal stress models. Pediatr Res 2007; 62:240-5;PMID:17622962; http://dx.doi.org/10.1203/ PDR.0b013e3180db2949
61. Barreau F, Salvador-Cartier C, Houdeau E, Bueno L, Fioramonti J. Long-term alterations of colonic nerve-mast cell interactions induced by neonatal maternal deprivation in rats. Gut 2008; 57:582-90;PMID:18194988; http://dx.doi.org/10.1136/ gut.2007.126680
62. Prorok-HamonM, Friswell MK, AlswiedA, Roberts CL, Song F, Flanagan PK, et al. Colonic mucosaassociated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer. Gut 2014; 63:761-70; PMID:23846483
63. Brassesco MS, Xavier DJ, Camparoto ML, Montaldi AP, de Godoy PR, Scrideli CA, Tone LG, SakamotoHojo ET. Cytogenetic instability in childhood acute lymphoblastic leukemia survivors. J Biomed Biotechnol 2011; 2011;PMID:20871850; http:// dx.doi.org/10.1155/2011/230481
64. Jenney ME, Levitt GA. The quality of survival after childhood cancer. Eur J Cancer 2002; 38:1241-50, discussion 1251-3;PMID:12044511; http://dx.doi. org/10.1016/S0959-8049(02) 00091-6
65. Rice SC, VacekP, Homans AH, MessierT, RiversJ, KendallH, Finette BA. Genotoxicity of therapeutic intervention in children with acute lymphocytic leukemia. Cancer Res 2004; 64:4464-71; PMI D:15231655; http://dx.doi.org/10.1158/0008-5472.CAN-03-3940
66. Nakachi K, Hayashi T, Hamatani K, Eguchi H, Kusunoki Y. Sixty years of follow-up of Hiroshima and Nagasaki survivors: current progress in molecular epidemiology studies. Mutat Res 2008; 659:109-17;PMID:18406659; http://dx.doi.org/10.1016/j. mrrev.2008.02.001
67. van der Flier LG, Clevers H. Stem cells, selfrenewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 2009; 71:241-60; PMID:18808327; http://dx.doi.org/10.1146/ annurev.physiol.010908.163145
68. Dekaney CM, Gulati AS, Garrison AP, Helmrath MA, Henning SJ. Regeneration of intestinal stem/ progenitor cells following doxorubicin treatment of mice. Am J Physiol Gastrointest Liver Physiol 2009; 297:G461-70;PMID:19589945; http://dx.doi. org/10.1152/ajpgi.90446.2008
69. van Es JH, Jay P, Gregorieff A, van Gijn ME, Jonkheer S, Hatzis P, Thiele A, van den Born M, BegthelH, BrabletzT, et al. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol 2005; 7:381-6;PMI D:15778706; http:// dx.doi.org/10.1038/ncb1240
70. Garabedian EM, Roberts LJ, McNevin MS, Gordon JI. Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice. J Biol Chem 1997; 272:23729-40;PMID:9295317; http:// dx.doi.org/10.1074/jbc.272.38.23729
71. BastideP, DaridoC, PannequinJ, KistR, RobineS, Marty-Double C, Bibeau F, Scherer G, Joubert D, Hollande F, et al. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. J Cell Biol 2007; 178:635-48;PMID:17698607; http://dx.doi.org/10.1083/ jcb.20 0704152
72. ZhaoJ, de VeraJ, NarushimaS, Beck EX, Palencia S, Shinkawa P, Kim KA, Liu Y, Levy MD, Berg DJ, et al. R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. Gastroenterology 2007; 132:1331-43; PMID:17408649; http://dx.doi.org/10.1053/j. gastro.2007.02.001
73. King SL, Mohiuddin JJ, Dekaney CM. Paneth cells expand from newly created and preexisting cells during repair after doxorubicin-induced damage. Am J Physiol Gastrointest Liver Physiol 2013; 305:G151-62;PMID:23660502; http://dx.doi.org/10.1152/ ajpgi.00441.2012
74. Heyman M, Desjeux JF. Significance of intestinal food protein transport. J Pediatr Gastroenterol Nutr 1992; 15:48-57;PMID:1403450; http://dx.doi. org/10.1097/00005176-199207000-00008
75. Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M, Neal KR. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47:804-11; PMID:11076879; http://dx.doi.org/10.1136/ gut.47.6.804
76. Salim SY, Söderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis 2011; 17:362-81; PMID:20725949; http://dx.doi.org/10.1002/ ibd.21403
77. PendersJ, ThijsC, van den Brandt PA, Kummeling I, Snijders B, Stelma F, Adams H, van Ree R, Stobberingh EE. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 2007; 56:661-7;PMID:17047098; http://dx.doi.org/10.1136/ gut.2006.100164
78. Hong PY, Lee BW, Aw M, Shek LP, Yap GC, Chua KY, Liu WT. Comparative analysis of fecal microbiota in infants with and without eczema. PLoS One 2010; 5:e9964;PMID:20376357; http://dx.doi. org/10.1371/journal.pone.0009964
79. Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin Exp Immunol 2010; 160:1-9;PMID:20415844; http://dx.doi. org/10.1111/j.1365-2249.2010.04139.x
80. Benard A, Desreumeaux P, Huglo D, Hoorelbeke A, Tonnel AB, Wallaert B. Increased intestinal permeability in bronchial asthma. J Allergy Clin Immunol 1996; 97:1173-8;PMID:8648009; http:// dx.doi.org/10.1016/S0091-6749(96)70181-1
81. HijaziZ, Molla AM, Al-HabashiH, Muawad WM, Molla AM, Sharma PN. Intestinal permeability is increased in bronchial asthma. Arch Dis Child 2004; 89:227-9;PMID:14977697; http://dx.doi. org/10.1136/adc.2003.027680
82. Blaser MJ, Falkow S. What are the consequences of the disappearing human microbiota? Nat Rev Microbiol 2009; 7:887-94;PMID:19898491; http:// dx.doi.org/10.1038/nrmicro2245