The influence of the young microbiome on inflammatory diseases-Lessons from animal studies

Birth Defects Research Part C - Embryo Today: Reviews

Volumn 105, Issue 4, 2015, Pages 278-295

  Bendtsen, Katja M ^a   Fisker, Line ^a   Hansen, Axel K ^a   Hansen, Camilla H F ^a   Nielsen, Dennis S ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Allergy; Colonization; Gut microbiota; Microbiome; Respiratory disease; Type 1 diabetes

Indexed keywords

ANTIBIOTIC AGENT; IMMUNOGLOBULIN E; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 9; KANAMYCIN; MYELOID DIFFERENTIATION FACTOR 88; NONSTEROID ANTIINFLAMMATORY AGENT; OXAZOLONE; POLYMYXIN B; PREBIOTIC AGENT; PROBIOTIC AGENT; STREPTOMYCIN; TESTOSTERONE; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 5; VANCOMYCIN;

AIRWAY OBSTRUCTION; ALLERGIC ASTHMA; ANTIBIOTIC THERAPY; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ATOPIC DERMATITIS; BACTERIAL COLONIZATION; EARLY INTERVENTION; ESCHERICHIA COLI; EXPERIENCE; HELICOBACTER PYLORI; IMMUNE SYSTEM; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; INFLAMMATORY DISEASE; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE FLORA; LACTOCOCCUS LACTIS; MICROBIOME; NONHUMAN; OBESITY; PERINATAL PERIOD; PREGNANCY; PRIORITY JOURNAL; RESPIRATORY TRACT DISEASE; RISK FACTOR; ANIMAL; DISEASE MODEL; FEMALE; HUMAN; MICROBIOLOGY; PHYSIOLOGY;

ANIMALS; DISEASE MODELS, ANIMAL; FEMALE; GASTROINTESTINAL MICROBIOME; HUMANS; IMMUNE SYSTEM; INFLAMMATION; INFLAMMATORY BOWEL DISEASES; PREGNANCY;

EID: 84955646579     PISSN: 1542975X     EISSN: 15429768     Source Type: Journal    
DOI: 10.1002/bdrc.21116     Document Type: Article

References (119)

1. Abdelouhab K, Rafaa H, Toumia R, et al. 2012. Mucosal intestinal alteration in experimental colitis correlates with nitric oxide production by peritoneal macrophages: effect of probiotics and prebiotics. Immunopharmacol Immunotoxicol 34:590-597.
2. Abrahamsson TR, Andersson AF, Bjorksten B, et al. 2011. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 129:434-440.
3. Alkanani AK, Hara N, Lien E, et al. 2014. Induction of diabetes in the RIP-B7.1 mouse model is critically dependent on TLR3 and MyD88 pathways and is associated with alterations in the intestinal microbiome. Diabetes 63:619-631
4. Aranda R, Sydora BC, McAllister PL, et al. 1997. Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients. J Immunol 158:3464-3473.
5. Arnold IC, Reuter S, Martin H, et al. 2011. Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J Clin Investig 121:6.
6. De Benedetto A, Agnihothri R, McGirt LY, et al. 2009. Atopic dermatitis: a disease caused by innate immune defects? J Investig Dermatol 129:14-30.
7. Bisgaard H, Li N, Bonnelykke K, et al. 2011. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 128:646-652.
8. Björkstén BNP, Sepp E, Mikelsaar M. 1999. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 29:342-346.
9. Blaser MJ, Reibman J. 2008. Does Helicobacter pylori protect against asthma and allergy? Gut 57:561-567.
10. Blaser MJ. 2009. What are the consequences of the disappearing human microbiota? Nat Rev 7:887-894.
11. Blaser MJ. 2011. Stop the killing of beneficial bacteria. Nature 476:393-394.
12. Blümer N, Sel S, Virna S, et al. 2007. Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring. Clin Exp Allergy 37:348-357.
13. Boguniewicz M, Leung D. 2010. Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol 125:4-13.
14. Bohn E, Bechtold O, Zahir N, et al. 2006. Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains. Common patterns and bacteria specific signatures. Inflamm Bowel Dis 12:853-862.
15. Brugman S, Klatter FA, Visser JTJ, et al. 2006. 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 49:2105-2108.
16. Calcinaro F, Dionisi S, Marinaro M, et al. 2005. Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia 48:1565-1575.
17. Candon S, Perez-Arroyo A, Marquet C, et al. 2015. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes. PLoS One 10:e0125448.
18. Carroll IM, Andrus JM, Bruno-Bárcena JM, et al. 2007. Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am J Physiol Gastrointest Liver Physiol 293:G729-G738.
19. Cates EC, Fattouh R, Wattie J, et al. 2004. Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism. J Immunol 173:6384-6392.
20. Chapat LCK, Dubois B, Bourdet-Sicard R, Kaiserlian D. 2004. Lactobacillus casei reduces CD8+ T cell-mediated skin inflammation. Eur J Immunol 34:2520-2528.
21. Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M. 2014. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 104:Unit 15.25.
22. Chauhan R, Vasanthakumari AS, Panwar H, et al. 2014. Amelioration of colitis in mouse model by exploring antioxidative potentials of an indigenous probiotic strain of Lactobacillus fermentum Lf1. Biomed Res Int 2014:206732.
23. Cho I, Yamanishi S, Cox L, et al. 2012. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488:621-626.
24. Desbonnet L, Clarke G, ÓSullivan O, et al. 2015. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. Brain Behavior and Immunity 48:165-173.
25. Dogra S, Sakwinska O, Soh SE, et al. 2015. Dynamics of infant gut microbiota are influenced by delivery mode and gestational duration and are associated with subsequent adiposity. MBio 6:e02419-e02414.
26. Dominguez-Bello MG, Costello EK, Contreras M, et al. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 107:11971-11975.
27. Forsythe P, Inman MD, Bienenstock J. 2007. Oral treatment with live Lactobacillus reuteri inhibits the allergic airway response in mice. Am J Respir Crit Care Med 175:561-569.
28. Fujimura KE, Demoor T, Rauch M, et al. 2014. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proc Natl Acad Sci USA 111:805-810.
29. Fujiwara RTN, Watanabe J, Sonoyama K. 2010a. Maternal consumption of fructo-oligosaccharide diminishes the severity of skin inflammation in offspring of NC/Nga mice. Br J Nutr 103:530-538.
30. Fujiwara R, Sasajima N, Takemura N, et al. 2010b. 2, 4-Dinitrofluorobenzene-induced contact hypersensitivity response in NC/Nga mice fed fructo-oligosaccharide. J Nutr Sci Vitaminol 56:260-265.
31. Funda DP, Kaas A, Bock H, et al. 1999. Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev 15:323-327.
32. Gale EA, Gillespie KM. 2001. Diabetes and gender. Diabetologia 44:3-15.
33. Gale EA. 2002. The rise of childhood type 1 diabetes in the 20th century. Diabetes 51:3353-336.
34. Garrett WS, Glimcher LH. 2009. T-bet-/- RAG2-/- ulcerative colitis: the role of T-bet as a peacekeeper of host-commensal relationships. Cytokine 48:144-147.
35. Garrett WS, Gallini CA, Yatsunenko T, et al. 2010. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8:292-300.
36. Gold M, Marsolais D, Blanchet MR. 2015. Mouse models of allergic asthma. Methods Mol Biol 1220:503-519.
37. Gronlund MM, Lehtonen OP, Eerola E, Kero P. 1999. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J. Pediatr. Gastroenterol 28:19-25.
38. Greiner TU, Hyötyläinen T, Knip M, et al. 2014. The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice. PLoS One 9:e110359.
39. Hansen AK, Ling F, Kaas A, et al. 2006. Diabetes preventive gluten-free diet decreases the number of caecal bacteria in non-obese diabetic mice. Diabetes Metab Res Rev 22:220-225.
40. Hansen CHF, Andersen LSF, Krych ł, Metzdorff SB, Skov S, Nielsen DS, Buschard K, Hansen LH, Hansen AK. 2014a. Mode of delivery shapes gut colonization pattern and modulates regulatory immunity in mice. J Immunology 193:1213-1222.
41. Hansen CH, Krych L, Buschard K, et al. 2014b. A maternal gluten-free diet reduces inflammation and diabetes incidence in the offspring of NOD mice. Diabetes 63:2821-2832.
42. Hansen CHF, Krych L, Nielsen DS, et al. 2012a. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia 55:2285-2294.
43. Hansen CHF, Nielsen DS, Kverka M, et al. 2012b. Patterns of early gut colonization shape future immuneresponses of the host. PLoS One 7:e34043.
44. Herbst T, Sichelstiel A, Schär C, et al. 2011. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am J Respir Crit Care Med 15:198-205.
45. Hildebrand F, Brinkman B, Yunta RG, et al. 2013. Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice. Genome Biol 14:R4 doi:10.1186/gb-2013-14-1-r4.
46. Hill DA, Siracusa MC, Abt MC, et al. 2012. Commensal bacterial-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18:538-546.
47. Hogenkamp A, van Vlies N, Garssen J. 2015. Supplementing pregnant mice with a specific mixture of nondigestible oligosaccharides reduces symptoms of allergic asthma in male offspring. J Nutr 145:640-646.
48. Holgate ST. 2008. Pathogenesis of asthma. Clin Exp Allergy 38:872-897.
49. Hunt JR, Adams VC, Rook GA, Brunet LR. 2005. Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model. Clin Exp Allergy 35:685-690.
50. Inoue RNA, Fukushima Y, Ushida K. 2007. Oral treatment with probiotic Lactobacillus johnsonii NCC533 (La1) for a specific part of the weaning period prevents the development of atopic dermatitis induced after maturation in model mice, NC/Nga. Br J Dermatol 156:499-509.
51. Ivanov II, Frutos RDEL, Manel N, et al. 2008. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4:337-349.
52. Jergens AE, Wilson-Welder JH, Dorn A, et al. 2007. Helicobacter bilis triggers persistent immune reactivity to antigens derived from the commensal bacteria in gnotobiotic C3H/HeN mice. Gut 56:934-940.
53. Jin H, He R, Oyoshi M, Geha R. 2009. Animal models of atopic dermatitis. J Invest Dermatol 129:31-40.
54. Kabat AM, Srinivasan N, Maloy KJ. 2014. Modulation of immune development and function by intestinal microbiota. Trends Immunol 35:507-517.
55. Kawada M, Arihiro A, Mizoguchi E. 2007. Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease. World J Gastroenterol 13:5581-5593.
56. King C, Sarvetnick N. 2011. The incidence of type-1 diabetes in NOD mice is modulated by restricted flora not germ-free conditions. PLoS One 6:e17049.
57. Kim N, Kunisawa J, Kweon MN, et al. 2007. Oral feeding of Bifidobacterium bifidum (BGN4) prevents CD4(+) CD45RB(high) T cell-mediated inflammatory bowel disease by inhibition of disordered T cell activation. Clin Immunol 123:30-39.
58. King AJ. The use of animal models in diabetes research. British Journal of Pharmacology. 2012;166:877-894.
59. Kirjavainen PV, Salminen SJ, Isolauri E. 2002. Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Gut 51:51-55.
60. Kozyrskyj AL, Ernst P, Becker AB. 2007. Increased risk of childhood asthma from antibiotic use in early life. Chest 131:1753-1759.
61. Kristensen MB, Metzdorff SB, Bergström A, et al. 2015. Neonatal microbial colonization in mice promotes prolonged dominance of CD11b+Gr-1+ cells and accelerated establishment of the CD4+ T cell population in the spleen. Immunity Inflam Dis 3:309-320.
62. Kriegel MA, Sefik E, Hill JA, et al. 2011. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc Natl Acad Sci USA 108:11548-11553.
63. Krych L, Nielsen DS, Hansen AK, Hansen CHF. 2015. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD Mice. Gut Microbes 6:101-109.
64. Kuo SM, Merhige PM, Hagey LR . (2013) The Effect of Dietary Prebiotics and Probiotics on Body Weight, Large Intestine Indices, and Fecal Bile Acid Profile in Wild Type and IL10-/- Mice. PLoS ONE 8:e60270.
65. Lai CK, Crane J, Foliaki S, et al. 2009. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 64:476-483.
66. Lightfoot YL, Selle K, Yang T, et al. 2015. SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. EMBO J 34:881-895.
67. Lundberg R, Pang W, Nielsen DS, et al. 2012. Gastrointestinal microbiota and local inflammation during oxazolone-induced dermatitis in BALB/cA mice. Compar Med 62:371-380.
68. Ly NPLA, Gold DR, Celedón JC. 2011. Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol 127:1087-1094.
69. Lyons AO, Mahony F, O'Brien F, et al. 2009. Bacterial strain-specific induction of Foxp31 T regulatory cells is protective in murine allergy models. Clin Exp Allergy 40:811-819.
70. Mah KW, Lee BW, van Bever HP, et al. 2006. Distinct pattern of commensal gut microbiota in toddlers with eczema. Int Arch Allergy Immunol 140:157-163.
71. Man MQ, Lee SH, Man M, et al. 2008. Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. J Invest Dermatol 128:79-86.
72. Marra F, Marra CA, Richardson K, et al. 2009. Antibiotic use in children is associated with increased risk of asthma. Pediatrics 123:1003-1010.
73. Matsuda H, Geba GP, Sperl J, et al. 1997. Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol 9:461-466.
74. Matsumoto K, Oyobikawa M, Ohshima H, Tagami H. 2004. Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments. Skin Res Technol 10:122-129.
75. McLoughlin RM. 2011. Influence of gastrointestinal commensal bacteria on the immune responses that mediate allergy and asthma. J Allergy Clin Immunol 127:1097-1107.
76. Molodecky NA, Soon IS, Rabi DM, et al. 2012. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46-54.
77. Murri M, Leiva I, Gomez-Zumaquero JM, et al. 2013. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med 11:46.
78. Musso G, Gambino R, Cassader M. 2010. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care 33:2277-2284.
79. Nagano Y, Itoh K, Honda K. 2012. The induction of Treg cells by gut-indigenous Clostridium. Curr Opin Immunol 24:392-397.
80. Nakae S, Yu M, Monteforte R, et al. 2007. Mast cell-derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice. J Allergy Clin Immunol 120:48-55.
81. Natividad JM, Petit V, Huang X, et al. 2012. Commensal and probiotic bacteria influence intestinal barrier function and susceptibility to colitis in Nod1-/-; Nod2-/- mice. Inflamm Bowel Dis 18:1434-1446.
82. Nielsen DS, Krych L, Buschard K, et al. 2014. Beyond genetics. Influence of dietary factors and gut microbiota on type 1 diabetes. FEBS Lett 588:4234-4243.
83. Nishitani Y, Tanoue T, Yamada K, et al. 2009. Lactococcus lactis subsp. cremoris FC alleviates symptoms of colitis induced by dextran sulfate sodium in mice. Int Immunopharmacol 9:1444-1451.
84. Norman JM, Handley SA, Baldridge MT, et al. 2015. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160:447-460.
85. Noverr MC, McDonald RA, McKenzie AN, Huffnagle GB. 2005. Development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13. Infect Immun 73:30-38.
86. Noverr MC, Toews GB, Huffnagle GB. 2004. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun 72:4996-5003.
87. Olszak T, Zeissig S, Vera MP, et al. 2012. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336:489-493.
88. Org E, Parks BW, Joo JWJ, et al. 2015. Genetic and environmental control of host-gut microbiota interactions. Genome Res 25:112.
89. Pang W, Wang H, Shi L, et al. 2013. Immunomodulatory effects of Escherichia coli ATCC 25922 on allergic airway inflammation in a mouse model. PLoS One 8:e59174.
90. Penders J, Thijs C, Vink C, et al. 2006. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 118:511-521.
91. Penders J, Thijs C, Zimmermann K, et al. 2014. New insights into the hygiene hypothesis in allergic diseases. Mediation of sibling and birth mode effects by the gut microbiota. Gut Microbes 5:239-244.
92. Perše M, Cerar A. 2012. Dextran sodium sulfate colitis mouse model: traps and tricks. J Biomed Biotechnol 2012:718617.
93. Philippe D, Heupel E, Blum-Sperisen S, Riedel CU. 2011. Treatment with Bifidobacterium bifidum 17 partially protects mice from Th1-driven inflammation in a chemically induced model of colitis. Int J Food Microbiol 149:45-49.
94. Podolsky DK. 2002. Inflammatory bowel disease. N Engl J Med 347:417-429.
95. Robinson CJY. 2010. Antibiotic administration alters the community structure of the gastrointestinal micobiota. Gut Microbes 1:279-284.
96. Round JL, Mazmanian SK. 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9:313-323.
97. Russell SL, Hartmann M, Willing BP, et al. 2012. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep 13:440-447.
98. Russell SL, Willing BP, Thorson L, et al. 2013. Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Gut Microbes 4:158-164.
99. Salminen S, Isolauri E, Scalabrin D. 2015. Early gut colonization with lactobacilli and staphylococcus in infants: the hygiene hypothesis extended. J Pediatr Gastroenterol Nutr. Epub ahead of print. http://dx.doi.org/10.1097/MPG.0000000000000925
100. Sasajima NOT, Takemura N, Fujiwara R, et al. 2010. Role of intestinal Bifidobacterium pseudolongum in dietary fructo-oligosaccharide inhibition of 2, 4-dinitrofluorobenzene-induced contact hypersensitivity in mice. Br J Nutr 103:539-548.
101. Satokari R, Laitinen K, Salminen S, Isolauri E. 2009. Bifidobacterium and Lactobacillus DNA in the human placenta. Lett Appl Microbiol 48:8-12.
102. Sevelsted J, Bønnelykke K, Bisgaard H. 2015. Cesarean section and chronic immune disorders. Pediatrics 135:92-98.
103. Shah MMSM, Yamashita H, Tanaka H, et al. 2012. Lactobacillus acidophilus strain L-92 induces CD4(+)CD25(+)Foxp3(+) regulatory T cells and suppresses allergic contact dermatitis. Biol Pharm Bull 35:612-616.
104. Srutkova D, Schwarzer M, Hudcovic T, et al. 2015. Bifidobacterium longum CCM 7952 promotes epithelial barrier function and prevents acute DSS-induced colitis in strictly strain-specific manner. PLoS One 10:e0134050.
105. Stepankova R, Powrie F, Kofronova O, et al. 2007. Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RB high CD4+ T cells. Inflamm Bowel Dis 13:1202-1211.
106. Strachan DP. 1989. Hay-fever, hygiene, and household size. Br Med J 299:1259-1260.
107. Suto HM, Mitsuishi K, Hira K, et al. 1999. NC/Nga mice: a mouse model for atopic dermatitis. Int Arch Allergy Immunol 120:70-75.
108. Tanaka AJK, Benyacoub J, Prioult G, et al. 2009. Oral supplementation with Lactobacillus rhamnosus CGMCC 1.3724 prevents development of atopic dermatitis in NC/NgaTnd mice possibly by modulating local production of IFN-gamma. Exp Dermatol 18:1022-1027.
109. Tougaard P, Skov S, Pedersen AE, et al. 2015. TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition. Eur J Immunol 45:865-875.
110. Wang Z, Gleichmann H. 1998. GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes 47:50-56.
111. Watanabe J, Sasajima N, Ito S, Sonoyama K. 2010. Administration of antibiotics during infancy promoted the development of atopic dermatitis-like skin lesions in NC/Nga mice. Biosci Biotechnol Biochem 74:358-363.
112. Watanabe JSN, Aramaki A, Sonoyama K. 2008. Consumption of fructo-oligosaccharide reduces 2, 4-dinitrofluorobenzene-induced contact hypersensitivity in mice. Br J Nutr 100:339-346.
113. Watanabe S, Arase S, Okamatsu H, et al. 2003. Differences in fecal microflora between patients with atopic dermatitis and healthy control subjects. J Allergy Clin Immunol 111:579-591.
114. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu CY, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV . 2008 Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455:1109-1113.
115. Williams H, von Mutius E, Cookson W, Anderson HR. 2008. Is eczema really on the increase worldwide? J Allergy Clin Immunol 121:947-954.
116. Xavier RJ, Podolsky DK. 2007. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427-434.
117. Yach D, Hawkes C, Gould CL, Hofman KJ. 2004. The global burden of chronic diseases: overcoming impediments to prevention and control. JAMA 291:2616-22.
118. Yatsunenko T, Rey FE, Manary MJ, et al. 2012. Human gut microbiome viewed across age and geography. Nature 486:222-227.
119. Yurkovetskiy L, Yurkovetskiy L, Burrows M, et al. 2013. Gender bias in autoimmunity is influenced by microbiota. Immunity 39:400-412.