Background. The hygiene hypothesis suggests that high hygiene standards have led to an immune dysfunction and an increase in allergic diseases. Farming-related exposures are associated with a decreased risk of asthma. Since the gut microbiota may be a pivotal component in the hygiene hypothesis, we studied whether perinatal exposure to pets, doctor's diagnosed wheezy bronchitis (WB), and compositional changes in the gut microbiota are interrelated among urban infants. Methods. Data were collected prospectively from a mother-infant nutrition study. Data on perinatal pet ownership, WB, and the microbiota composition of faecal samples of the infants assessed by quantitative PCR at 1 month were compared. Results. None of the 30 infants exposed to pets had suffered from WB by 24 months, whereas 15 of the 99 (15%) nonexposed infants had had WB ( ). The counts of Bifidobacterium longum were higher in samples ( ) from nonwheezing infants with pet exposure compared to those ( ) in wheezing infants without pet exposure (8.59/10.44 versus 5.94/9.86, resp. (median/upper limit of range, bacteria(log)/g of stool); ). B. breve was more abundant in the wheezing infants ( ). 1. Introduction The development of asthma and allergic diseases is a result of complex interactions between genetic predisposition and multiple environmental influences [1]. The hygiene hypothesis, first proposed by Strachan in 1989 [2] and subsequently supported by epidemiological studies [3], suggests that the higher hygiene standards adopted during the last few decades have led to dysfunction in the immune system, giving rise to allergic and autoimmune diseases as seen especially in affluent societies. Modern infants living in the developed countries may thus lack stimulation of the mucosal immune system sufficient to generate a tolerogenic immune milieu and be prone to develop diseases of inflammatory origin. In support of such a conception, differences in the neonatal gut microbiota have been shown to precede the development of atopy; for example, infants in whom atopy is developing harbour fewer bifidobacteria than their nonatopic peers [4]. The original hygiene hypothesis has been extended to a microbiota hypothesis emphasising the importance of the indigenous intestinal microbiota [5]. Farming-related exposures such as exposure to animal sheds and raw milk consumption have been shown to protect against the development of asthma and allergies [3]. Children living on farms are exposed to a wide range of microbes, and the diversity of microbial exposure is inversely associated with the risk of
References
[1]
S. M. Ho, “Environmental epigenetics of asthma: an update,” Journal of Allergy and Clinical Immunology, vol. 126, no. 3, pp. 453–465, 2010.
[2]
D. P. Strachan, “Hay fever, hygiene, and household size,” British Medical Journal, vol. 299, no. 6710, pp. 1259–1260, 1989.
[3]
E. von Mutius and D. Vercelli, “Farm living: effects on childhood asthma and allergy,” Nature Reviews Immunology, vol. 10, no. 12, pp. 861–868, 2010.
[4]
M. Kalliom?ki, P. Kirjavainen, E. Eerola, P. Kero, S. Salminen, and E. Isolauri, “Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing,” Journal of Allergy and Clinical Immunology, vol. 107, no. 1, pp. 129–134, 2001.
[5]
S. Rautava, O. Ruuskanen, A. Ouwehand, S. Salminen, and E. Isolauri, “The hygiene hypothesis of atopic disease—an extended version,” Journal of Pediatric Gastroenterology and Nutrition, vol. 38, no. 4, pp. 378–388, 2004.
[6]
M. J. Ege, M. Mayer, A. C. Normand, et al., “Exposure to environmental micro-organisms and childhood asthma,” The New England Journal of Medicine, vol. 364, pp. 701–709, 2011.
[7]
R. M. Maier, M. W. Palmer, G. L. Andersen et al., “Environmental determinants of and impact on childhood asthma by the bacterial community in household dust,” Applied and Environmental Microbiology, vol. 76, no. 8, pp. 2663–2667, 2010.
[8]
K. E. Fujimura, C. C. Johnson, D. R. Ownby et al., “Man's best friend? the effect of pet ownership on house dust microbial communities,” Journal of Allergy and Clinical Immunology, vol. 126, no. 2, pp. 410.e3–412.e3, 2010.
[9]
D. Oberle, E. von Mutius, and R. von Kries, “Childhood asthma and continuous exposure to cats since the first year of life with cats allowed in the child's bedroom,” Allergy, vol. 58, no. 10, pp. 1033–1036, 2003.
[10]
S. T. Remes, J. A. Castro-Rodriguez, C. J. Holberg, F. D. Martinez, and A. L. Wright, “Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy,” Journal of Allergy and Clinical Immunology, vol. 108, no. 4, pp. 509–515, 2001.
[11]
E. Bergroth, S. Remes, J. Pekkanen, T. Kauppila, G. Büchele, and L. Keski-Nisula, “Respiratory tract illnesses during the first year of life: effect of dog and cat contacts,” Pediatrics, vol. 130, no. 2, pp. 211–220, 2012.
[12]
P. I. Pfefferle, G. Büchele, N. Blümer et al., “Cord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE study,” Journal of Allergy and Clinical Immunology, vol. 125, no. 1–3, pp. 108.e3–115.e3, 2010.
[13]
C. Roduit, J. Wohlgensinger, R. Frei et al., “Prenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis,” Journal of Allergy and Clinical Immunology, vol. 127, no. 1, pp. 179.e1–185.e1, 2011.
[14]
K. Laitinen, T. Poussa, and E. Isolauri, “Probiotics and dietary counselling contribute to glucose regulation during and after pregnancy: a randomised controlled trial,” British Journal of Nutrition, vol. 101, no. 11, pp. 1679–1687, 2009.
[15]
Nordic Working Group on Diet and Nutrition, “Nordic nutritional recommendations,” Scandinavian Journal of Nutrition, vol. 40, pp. 161–165, 1996.
[16]
W. Becker, N. Lyhne, A. N. Pedersen et al., “Nordic nutrition recommendations 2004—integrating nutrition and physical activity,” Scandinavian Journal of Nutrition, vol. 48, no. 4, pp. 178–187, 2004.
[17]
M. Nermes, J. M. Kantele, T. J. Atosuo, S. Salminen, and E. Isolauri, “Interaction of orally administered Lactobacillus rhamnosus GG with skin and gut microbiota and humoral immunity in infants with atopic dermatitis,” Clinical and Experimental Allergy, vol. 41, no. 3, pp. 370–377, 2011.
[18]
M. C. Collado, M. Derrien, E. Isolauri, W. M. de Vos, and S. Salminen, “Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly,” Applied and Environmental Microbiology, vol. 73, no. 23, pp. 7767–7770, 2007.
[19]
P. Kaufmann, A. Pfefferkorn, M. Teuber, and L. Meile, “Identification and quantification of Bifidobacterium species isolated from food with genus-specific 16S?rRNA-targeted probes by colony hybridization and PCR,” Applied and Environmental Microbiology, vol. 63, no. 4, pp. 1268–1273, 1997.
[20]
P. Marteau, P. Pochart, J. Doré, C. Béra-Maillet, A. Bernalier, and G. Corthier, “Comparative study of bacterial groups within the human cecal and fecal microbiota,” Applied and Environmental Microbiology, vol. 67, no. 10, pp. 4939–4942, 2001.
[21]
M. M. Rinne, M. Gueimonde, M. Kalliom?ki, U. Hoppu, S. J. Salminen, and E. Isolauri, “Similar bifidogenic effects of prebiotic-supplemented partially hydrolyzed infant formula and breastfeeding on infant gut microbiota,” FEMS Immunology and Medical Microbiology, vol. 43, no. 1, pp. 59–65, 2005.
[22]
T. Matsuki, K. Watanabe, J. Fujimoto et al., “Development of 16S rRNA-gene-targeted group-specific primers for the detection and identification of predominant bacteria in human feces,” Applied and Environmental Microbiology, vol. 68, no. 11, pp. 5445–5451, 2002.
[23]
J. Penders, C. Vink, C. Driessen, N. London, C. Thijs, and E. E. Stobberingh, “Quantification of Bifidobacterium spp., Escherichia coli and Clostridium difficile in faecal samples of breast-fed and formula-fed infants by real-time PCR,” FEMS Microbiology Letters, vol. 243, no. 1, pp. 141–147, 2005.
[24]
T. Matsuki, K. Watanabe, J. Fujimoto, T. Takada, and R. Tanaka, “Use of 16S?rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces,” Applied and Environmental Microbiology, vol. 70, no. 12, pp. 7220–7228, 2004.
[25]
M. G. Wise and G. R. Siragusa, “Quantitative detection of Clostridium perfringens in the broiler fowl gastrointestinal tract by real-time PCR,” Applied and Environmental Microbiology, vol. 71, no. 7, pp. 3911–3916, 2005.
[26]
O. G. Brakstad, K. Aasbakk, and J. A. Maeland, “Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene,” Journal of Clinical Microbiology, vol. 30, no. 7, pp. 1654–1660, 1992.
[27]
G. Loss, S. Bitter, J. Wohlgensinger et al., “Prenatal and early-life exposure alter expression of innate immunity genes: the PASTURE cohort study,” Journal of Allergy and Clinical Immunology, vol. 130, pp. 523–530, 2012.
[28]
R. P. Lauener, Birchler, J. Adamski, et al., “Expression of cD14 and Toll-like receptor 2 in farmers' and non-farmer's children,” The Lancet, vol. 360, pp. 465–466, 2002.
[29]
M. J. Ege, R. Frei, C. Bieli et al., “Not all farming environments protect against the development of asthma and wheeze in children,” Journal of Allergy and Clinical Immunology, vol. 119, no. 5, pp. 1140–1147, 2007.
[30]
J. Genuneit, “Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis,” Pediatric Allergy and Immunology, vol. 23, no. 6, pp. 509–518, 2012.
[31]
C. S. Murray, G. W. Tannock, M. A. Simon et al., “Fecal microbiota in sensitized wheezy and non-sensitized non-wheezy children: a nested case-control study,” Clinical and Experimental Allergy, vol. 35, no. 6, pp. 741–745, 2005.
[32]
Y. M. Sj?gren, M. C. Jenmalm, M. F. B?ttcher, B. Sj?krstén, and E. Sverremark-Ekstr?m, “Altered early infant gut microbiota in children developing allergy up to 5 years of age,” Clinical & Experimental Allergy, vol. 39, pp. 518–526, 2009.
[33]
C. F. Favier, E. E. Vaughan, W. M. de Vos, and A. D. L. Akkermans, “Molecular monitoring of succession of bacterial communities in human neonates,” Applied and Environmental Microbiology, vol. 68, no. 1, pp. 219–226, 2002.
[34]
A. P?rtty, M. Kalliom?ki, A. Endo, S. Salminen, and E. Isolauri, “Compositional development of Bifidobacterium and Lactobacilllus microbiota is linked with crying and fussin in early infancy,” PLoS One, vol. 7, no. 3, Article ID e32495, 2012.
[35]
S. L. Young, M. A. Simon, M. A. Baird et al., “Bifidobacterial species differentially affect expression of cell surface markers and cytokines of dendritic cells harvested from cord blood,” Clinical and Diagnostic Laboratory Immunology, vol. 11, no. 4, pp. 686–690, 2004.
[36]
O. Ménard, M. J. Butel, V. Gaboriau-Routhiau, and A. J. Waligora-Dupriet, “Gnotobiotic mouse immune response induced by Bifidobacterium sp. strains isolated from infants,” Applied and Environmental Microbiology, vol. 74, no. 3, pp. 660–666, 2008.