[ 1 ] von Mutius E. The rising trends in asthma and allergic disease. Clin Exp Allergy 1998;28(Suppl 5):45–9; discussion 50–1 链接1

[ 2 ] Williams H, Robertson C, Stewart A, Aït-Khaled N, Anabwani G, Anderson R, et alWorldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood. J Allergy Clin Immunol 1999;103(1):125–38 链接1

[ 3 ] Strachan D, Sibbald B, Weiland S, Ait-Khaled N, Anabwani G, Anderson HR, et alWorldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC). Pediatr Allergy Immunol 1997;8(4):161–8 链接1

[ 4 ] Braun-Fahrländer C, Gassner M, Grize L, Neu U, Sennhauser FH, Varonier HS, et alPrevalence of hay fever and allergic sensitization in farmer’s children and their peers living in the same rural community. Clin Exp Allergy 1999;29(1):28–34 链接1

[ 5 ] Braun-Fahrländer C, Riedler J, Herz U, Eder W, Waser M, Grize L, et alEnvironmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 2002;347(12):869–77 链接1

[ 6 ] Vrijheid M, Casas M, Bergström A, Carmichael A, Cordier S, Eggesbø M, et alEuropean birth cohorts for environmental health research. Environ Health Perspect 2012;120(1):29–37 链接1

[ 7 ] von Mutius E, Schmid S; the PASTURE Study Group. The PASTURE project: EU support for the improvement of knowledge about risk factors and preventive factors for atopy in Europe. Allergy 2006;61(4):407–13 链接1

[ 8 ] Schaub B, Vercelli D. Environmental protection from allergic diseases: from humans to mice and back. Curr Opin Immunol 2015;36:88–93 链接1

[ 9 ] Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science 2005;307(5717):1915–20 链接1

[10] Gao J, Wu H, Liu J. Importance of gut microbiota in health and diseases of new born infants. Exp Ther Med 2016;12(1):28–32 链接1

[11] Ring J. Akdis C, Behrendt H, Lauener RP, Schäppi G, Akdis M, et alDavos declaration: allergy as a global problem. Allergy 2012;67(2):141–3. Erratum in: Allergy 2012;67(5):712 链接1

[12] Riedler J, Braun-Fahrländer C, Eder W, Schreuer M, Waser M, Maisch S, et alExposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 2001;358(9288):1129–33 链接1

[13] Alfvén T, Braun-Fahrländer C, Brunekreef B, von Mutius E, Riedler J, Scheynius A, et alAllergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle—the PARSIFAL study. Allergy 2006;61(4):414–21 链接1

[14] Genuneit J, Büchele G, Waser M, Kovacs K, Debinska A, Boznanski A, et alThe GABRIEL advanced surveys: study design, participation and evaluation of bias. Paediatr Perinat Epidemiol 2011;25(5):436–47 链接1

[15] Wong GWK, Ko FWS, Hui DSC, Fok TF, Carr D, von Mutius E, et alFactors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey. BMJ 2004;329(7464):486 链接1

[16] Schröder PC, Li J, Wong GWK, Schaub B. The rural-urban enigma of allergy: what can we learn from studies around the world? Pediatr Allergy Immunol 2015;26(2):95–102 链接1

[17] Wong GWK, von Mutius E, Douwes J, Pearce N. Environmental determinants associated with the development of asthma in childhood. Int J Tuberc Lung Dis 2006;10(3):242–51.

[18] Osborn DA, Sinn JKH. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev 2007;(4):CD006475 链接1

[19] Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et alWorld allergy organization—McMaster University guidelines for allergic disease prevention (GLAD-P): probiotics. World Allergy Organ J 2015;8(1):4 链接1

[20] Forsberg A, West CE, Prescott SL, Jenmalm MC. Pre- and probiotics for allergy prevention: time to revisit recommendations? Clin Exp Allergy 2016;46(12):1506–21 链接1

[21] West CE. Probiotics for allergy prevention. Benef Microbes 2016;7(2):171–9 链接1

[22] Legatzki A, Rösler B, von Mutius E. Microbiome diversity and asthma and allergy risk. Curr Allergy Asthma Rep 2014;14(10):466 链接1

[23] Depner M, Ege MJ, Cox MJ, Dwyer S, Walker AW, Birzele LT, et alBacterial microbiota of the upper respiratory tract and childhood asthma. J Allergy Clin Immunol. Epub 2016 Jul 27 链接1

[24] Cui L, Morris A, Huang L, Beck JM, Twigg HL III, von Mutius E, et alThe microbiome and the lung. Ann Am Thorac Soc 2014;11(Suppl 4):S227–32 链接1

[25] Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, et alTemporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res 2012;22(5):850–9 链接1

[26] Findley K, Oh J, Yang J, Conlan S, Deming C, Meyer JA, et alTopographic diversity of fungal and bacterial communities in human skin. Nature 2013;498(7454):367–70 链接1

[27] McGuire MK, McGuire MA. Got bacteria? The astounding, yet not-so-surprising, microbiome of human milk. Curr Opin Biotechnol 2017;44:63–8 链接1

[28] Coca A, Cooke RA. On the classification of the phenomena of hypersensitiveness. J Immunol Baltim Md 1923;8(3):163–71.

[29] Blumenthal MN, Amos DB. Genetic and immunologic basis of atopic responses. Chest 1987;91(6):176S–84S 链接1

[30] Cookson WO. Genetic aspects of atopic allergy. Allergy 1998;53(s45):9–14 链接1

[31] Dold S, Wjst M, von Mutius E, Reitmeir P, Stiepel E. Genetic risk for asthma, allergic rhinitis, and atopic dermatitis. Arch Dis Child 1992;67(8):1018–22 链接1

[32] Edfors-Lubs ML. Allergy in 7000 twin pairs. Acta Allergol 1971;26(4):249–85 链接1

[33] Lluis A, Schedel M, Liu J, Illi S, Depner M, von Mutius E, et alAsthma-associated polymorphisms in 17q21 influence cord blood ORMDL3 and GSDMA gene expression and IL-17 secretion. J Allergy Clin Immunol 2011;127(6):1587–94.e6 链接1

[34] Leung TF, Ko FWS, Sy HY, Tsui SKW, Wong GWK. Differences in asthma genetics between Chinese and other populations. J Allergy Clin Immunol 2014;133(1):42–8 链接1

[35] Yu X, Yu C, Ren Z, Deng Y, Song J, Zhang H, et alGenetic variants of 17q21 are associated with childhood-onset asthma and related phenotypes in a northeastern Han Chinese population: a case-control study. Tissue Antigens 2014;83(5):330–6 链接1

[36] Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, et alA large-scale, consortium-based genomewide association study of asthma. N Engl J Med 2010;363(13):1211–21 链接1

[37] Zhang Y, Moffatt MF, Cookson WOC. Genetic and genomic approaches to asthma: new insights for the origins. Curr Opin Pulm Med 2012;18(1):6–13 链接1

[38] Nakayama T, Hirahara K, Onodera A, Endo Y, Hosokawa H, Shinoda K, et alTh2 cells in health and disease. Annu Rev Immunol. Epub 2016 Nov 28.

[39] von Mutius E. Environmental factors influencing the development and progression of pediatric asthma. J Allergy Clin Immunol 2002;109(6):S525–32 链接1

[40] Scholtens S, Postma D, Moffatt M, Panasevich S, Granell R, Henderson A, et alNovel childhood asthma genes interact with in utero and early-life tobacco smoke exposure. J Allergy Clin Immunol 2014;133(3):885–8 链接1

[41] Estelle F, Simons R, editors. Ancestors of allergy. New York: Global Medical Communications; 1994.

[42] Kabesch M, Schaal W, Nicolai T, von Mutius E. Lower prevalence of asthma and atopy in Turkish children living in Germany. Eur Respir J 1999;13(3):577–82 链接1

[43] Leung R. Asthma and migration. Respirology 1996;1(2):123–6 链接1

[44] Leung RC, Carlin JB, Burdon JG, Czarny D. Asthma, allergy and atopy in Asian immigrants in Melbourne. Med J Aust 1994;161(7):418–25.

[45] Zhao T, Wang A, Chen Y, Xiao M, Duo L, Liu G, et alPrevalence of childhood asthma, allergic rhinitis and eczema in Urumqi and Beijing. J Paediatr Child Health 2000;36(2):128–33 链接1

[46] von Mutius E. The environmental predictors of allergic disease. J Allergy Clin Immunol 2000;105(1):9–19 链接1

[47] Greer FR, Sicherer SH, Burks AW; American Academy of Pediatrics Committee on Nutrition, American Academy of Pediatrics Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008;121(1):183–91 链接1

[48] Dogaru CM, Nyffenegger D, Pescatore AM, Spycher BD, Kuehni CE. Breastfeeding and childhood asthma: systematic review and meta-analysis. Am J Epidemiol 2014;179(10):1153–67 链接1

[49] Strachan DP. Hay fever, hygiene, and household size. BMJ 1989;299(6710):1259–60 链接1

[50] Matricardi PM, Franzinelli F, Franco A, Caprio G, Murru F, Cioffi D, et alSibship size, birth order, and atopy in 11,371 Italian young men. J Allergy Clin Immunol 1998;101(4):439–44 链接1

[51] von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Reitmeir P, Thiemann HH. Skin test reactivity and number of siblings. BMJ 1994;308(6930):692–5 链接1

[52] Matricardi PM, Rosmini F, Ferrigno L, Nisini R, Rapicetta M, Chionne P, et alCross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis a virus. BMJ 1997;314(7086):999–1003 链接1

[53] Rosenlund H, Bergström A, Alm JS, Swartz J, Scheynius A, van Hage M, et alAllergic disease and atopic sensitization in children in relation to measles vaccination and measles infection. Pediatrics 2009;123(3):771–8 链接1

[54] Radon K, Windstetter D, Eckart J, Dressel H, Leitritz L, Reichert J, et alFarming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects. Clin Exp Allergy 2004;34(8):1178–83 链接1

[55] von Mutius E. Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence. Eur Respir J 2001;18(5):872–81 链接1

[56] Schaub B, Lauener R, von Mutius E. The many faces of the hygiene hypothesis. J Allergy Clin Immunol 2006;117(5):969–77 链接1

[57] Okada H, Kuhn C, Feillet H, Bach JF. The “hygiene hypothesis” for autoimmune and allergic diseases: an update. Clin Exp Immunol 2010;160(1):1–9 链接1

[58] Logan AC, Jacka FN, Craig JM, Prescott SL. The microbiome and mental health: looking back, moving forward with lessons from allergic diseases. Clin Psychopharmacol Neurosci 2016;14(2):131–47 链接1

[59] Prince BT, Mandel MJ, Nadeau K, Singh AM. Gut microbiome and the development of food allergy and allergic disease. Pediatr Clin North Am 2015;62(6):1479–92 链接1

[60] Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and the hygiene hypothesis. Science 2002;296(5567):490–4 链接1

[61] Yazdanbakhsh M, van den Biggelaar A, Maizels RM. Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends Immunol 2001;22(7):372–7 链接1

[62] von Mutius E, Sherrill DL, Fritzsch C, Martinez FD, Lebowitz MD. Air pollution and upper respiratory symptoms in children from East Germany. Eur Respir J 1995;8(5):723–8.

[63] von Mutius E, Weiland SK, Fritzsch C, Duhme H, Keil U. Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany. Lancet 1998;351(9106):862–6 链接1

[64] Vartiainen E, Petäys T, Haahtela T, Jousilahti P, Pekkanen J. Allergic diseases, skin prick test responses, and IgE levels in North Karelia, Finland, and the Republic of Karelia, Russia. J Allergy Clin Immunol 2002;109(4):643–8 链接1

[65] Bråbäck L, Breborowicz A, Julge K, Knutsson A, Riikjärv MA, Vasar M, et alRisk factors for respiratory symptoms and atopic sensitisation in the Baltic area. Arch Dis Child 1995;72(6):487–93 链接1

[66] Ege MJ, Herzum I, Büchele G, Krauss-Etschmann S, Lauener RP, Roponen M, et alPrenatal exposure to a farm environment modifies atopic sensitization at birth. J Allergy Clin Immunol 2008;122(2):407–12.e4 链接1

[67] Pfefferle PI, Büchele G, Blümer N, Roponen M, Ege MJ, Krauss-Etschmann S, et alCord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE study. J Allergy Clin Immunol 2010;125(1):108–15.e3 链接1

[68] von Mutius E, Illi S, Nicolai T, Martinez FD. Relation of indoor heating with asthma, allergic sensitisation, and bronchial responsiveness: survey of children in South Bavaria. BMJ 1996;312(7044):1448–50 链接1

[69] von Ehrenstein OS, von Mutius E, Illi S, Baumann L, Böhm O, von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 2000;30(2):187–93 链接1

[70] von Mutius E, Vercelli D. Farm living: effects on childhood asthma and allergy. Nat Rev Immunol 2010;10(12):861–8 链接1

[71] von Mutius E.[A traditional farming environment—a prophylactic factor against allergies]. Dtsch Med Wochenschr 2000;125(31–32):923. German.

[72] Vuitton DA, Dalphin JC. Hygiene and allergy: are farm microorganisms protective? J Mycol Med 2006;16(4):220–38 链接1

[73] Braun-Fahrländer CH. Allergic diseases in farmers’ children. Pediatr Allergy Immunol 2000;11(Suppl 13):19–22 链接1

[74] Kilpeläinen M, Terho EO, Helenius H, Koskenvuo M. Farm environment in childhood prevents the development of allergies. Clin Exp Allergy 2000;30(2):201–8 链接1

[75] Braun-Fahrländer C. The role of the farm environment and animal contact for the development of asthma and allergies. Clin Exp Allergy 2001;31(12):1799–803 链接1

[76] Campbell B, Raherison C, Lodge CJ, Lowe AJ, Gislason T, Heinrich J, et alThe effects of growing up on a farm on adult lung function and allergic phenotypes: an international population-based study. Thorax. Epub 2016 Sep 26 链接1

[77] Christensen SH, Timm S, Janson C, Benediktsdóttir B, Forsberg B, Holm M, et alA clear urban-rural gradient of allergic rhinitis in a population-based study in Northern Europe. Eur Clin Respir J 2016;3(1):33463 链接1

[78] Sudre B, Vacheyrou M, Braun-Fahrländer C, Normand AC, Waser M, Reboux G, et alHigh levels of grass pollen inside European dairy farms: a role for the allergy-protective effects of environment? Allergy 2009;64(7):1068–73 链接1

[79] Normand AC, Sudre B, Vacheyrou M, Depner M, Wouters IM, Noss I, et alAirborne cultivable microflora and microbial transfer in farm buildings and rural dwellings. Occup Environ Med 2011;68(11):849–55 链接1

[80] Waser M, Schierl R, von Mutius E, Maisch S, Carr D, Riedler J, et alDeterminants of endotoxin levels in living environments of farmers’ children and their peers from rural areas. Clin Exp Allergy 2004;34(3):389–97 链接1

[81] Waser M, von Mutius E, Riedler J, Nowak D, Maisch S, Carr D, et alExposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children. Allergy 2005;60(2):177–84 链接1

[82] Douwes J, Cheng S, Travier N, Cohet C, Niesink A, McKenzie J, et alFarm exposure in utero may protect against asthma, hay fever and eczema. Eur Respir J 2008;32(3):603–11 链接1

[83] Illi S, Depner M, Genuneit J, Horak E, Loss G, Strunz-Lehner C, et alProtection from childhood asthma and allergy in Alpine farm environments—the GABRIEL advanced studies. J Allergy Clin Immunol 2012;129(6):1470–7.e6 链接1

[84] Douwes J, Travier N, Huang K, Cheng S, McKenzie J, Le Gros G, et alLifelong farm exposure may strongly reduce the risk of asthma in adults. Allergy 2007;62(10):1158–65 链接1

[85] House JS, Wyss AB, Hoppin JA, Richards M, Long S, Umbach DM, et alEarly-life farm exposures and adult asthma and atopy in the Agricultural Lung Health Study. J Allergy Clin Immunol. Epub2016 Nov 11 链接1

[86] Schaub B, Liu J, Höppler S, Haug S, Sattler C, Lluis A, et alImpairment of T-regulatory cells in cord blood of atopic mothers. J Allergy Clin Immunol 2008;121(6):1491–9.e13 链接1

[87] Lluis A, Ballenberger N, Illi S, Schieck M, Kabesch M, Illig T, et alRegulation of TH17 markers early in life through maternal farm exposure. J Allergy Clin Immunol 2014;133(3):864–71 链接1

[88] Schröder PC, Illi S, Casaca VI, Lluis A, Böck A, Roduit C, et alA switch in regulatory T cells through farm exposure during immune maturation in childhood. Allergy. Epub 2016 Nov 17 链接1

[89] Eder W, von Mutius E. Hygiene hypothesis and endotoxin: what is the evidence? Curr Opin Allergy Clin Immunol 2004;4(2):113–7 链接1

[90] von Mutius E, Braun-Fahrländer C, Schierl R, Riedler J, Ehlermann S, Maisch S, et alExposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy 2000;30(9):1230–4 链接1

[91] Karadag B, Ege MJ, Scheynius A, Waser M, Schram-Bijkerk D, van Hage M, et alEnvironmental determinants of atopic eczema phenotypes in relation to asthma and atopic sensitization. Allergy 2007;62(12):1387–93 链接1

[92] Roussel S, Sudre B, Reboux G, Waser M, Buchele G, Vacheyrou M, et alExposure to moulds and actinomycetes in Alpine farms: a nested environmental study of the PASTURE cohort. Environ Res 2011;111(6):744–50 链接1

[93] Feng M, Yang Z, Pan L, Lai X, Xian M, Huang X, et alAssociations of early life exposures and environmental factors with asthma among children in rural and urban areas of Guangdong, China. Chest 2016;149(4):1030–41 链接1

[94] von Mutius E. Maternal farm exposure/ingestion of unpasteurized cow’s milk and allergic disease. Curr Opin Gastroenterol 2012;28(6):570–6 链接1

[95] Braun-Fahrländer C, von Mutius E. Can farm milk consumption prevent allergic diseases? Clin Exp Allergy 2011;41(1):29–35 链接1

[96] Waser M, Michels KB, Bieli C, Flöistrup H, Pershagen G, von Mutius E, et alInverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe. Clin Exp Allergy 2007;37(5):661–70 链接1

[97] Loss G, Apprich S, Waser M, Kneifel W, Genuneit J, Büchele G, et alThe protective effect of farm milk consumption on childhood asthma and atopy: the GABRIELA study. J Allergy Clin Immunol 2011;128(4):766–73.e4 链接1

[98] Barnes M, Cullinan P, Athanasaki P, MacNeill S, Hole AM, Harris J, et alCrete: does farming explain urban and rural differences in atopy? Clin Exp Allergy 2001;31(12):1822–8 链接1

[99] Wickens K, Lane JM, Fitzharris P, Siebers R, Riley G, Douwes J, et alFarm residence and exposures and the risk of allergic diseases in New Zealand children. Allergy 2002;57(12):1171–9 链接1

[100] Schaub B, Liu J, Höppler S, Schleich I, Huehn J, Olek S, et alMaternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol 2009;123(4):774–82.e5 链接1

[101] Brick T, Schober Y, Böcking C, Pekkanen J, Genuneit J, Loss G, et alw-3 fatty acids contribute to the asthma-protective effect of unprocessed cow’s milk. J Allergy Clin Immunol 2016;137(6):1699–706.e13 链接1

[102] Gehring U, Spithoven J, Schmid S, Bitter S, Braun-Fahrländer C, Dalphin JC, et alEndotoxin levels in cow’s milk samples from farming and non-farming families—the PASTURE study. Environ Int 2008;34(8):1132–6 链接1

[103] Peters M, Kauth M, Schwarze J, Körner-Rettberg C, Riedler J, Nowak D, et alInhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness. Thorax 2006;61(2):134–9 链接1

[104] Karvonen AM, Hyvärinen A, Rintala H, Korppi M, Täubel M, Doekes G, et alQuantity and diversity of environmental microbial exposure and development of asthma: a birth cohort study. Allergy 2014;69(8):1092–101 链接1

[105] Montel MC, Buchin S, Mallet A, Delbes-Paus C, Vuitton DA, Desmasures N, et alTraditional cheeses: rich and diverse microbiota with associated benefits. Int J Food Microbiol 2014;177:136–54 链接1

[106] Böcking C, Harb H, Ege MJ, Zehethofer N, Fischer K, Krauß J, et alBioavailability and allergoprotective capacity of milk-associated conjugated linoleic acid in a murine model of allergic airway inflammation. Int Arch Allergy Immunol 2014;163(3):234–42 链接1

[107] Rochat MK, Ege MJ, Plabst D, Steinle J, Bitter S, Braun-Fahrländer C, et alMaternal vitamin D intake during pregnancy increases gene expression of ILT3 and ILT4 in cord blood. Clin Exp Allergy 2010;40(5):786–94 链接1

[108] Podoprigora GI, [The gnotobiologic approach to the study of the body’s non-specific resistance to infection]. Arkh Patol 1976;38(3):77–85. Russian.

[109] Dubos RJ, Schaedler RW. The effect of the intestinal flora on the growth rate of mice, and on their susceptibility to experimental infections. J Exp Med 1960;111(3):407–17 链接1

[110] Hanna MG, Nettesheim P, Richter CB, Tennant RW. The variable influence of host microflora and intercurrent infections on immunological competence and carcinogenesis. Isr J Med Sci 1973;9(3):229–38.

[111] Glaister JR. Factors affecting the lymphoid cells in the small intestinal epithelium of the mouse. Int Arch Allergy Appl Immunol 1973;45(5):719–30 链接1

[112] Ferguson A, Parrott DMV. The effect of antigen deprivation on thymus-dependent and thymus-independent lymphocytes in the small intestine of the mouse. Clin Exp Immunol 1972;12(4):477–88.

[113] Eloy R, Vuitton D, Garaud JC, Vaultier JP, Klein M, Grenier JF. [Peyer’s patches and cellular immunity]. Biol Gastroenterol (Paris) 1975;8(1):73–86. French.

[114] Molloy J, Allen K, Collier F, Tang MLK, Ward AC, Vuillermin P. The potential link between gut microbiota and IgE-mediated food allergy in early life. Int J Environ Res Public Health 2013;10(12):7235–56 链接1

[115] Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001;291(5505):881–4 链接1

[116] Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nuñez G, et alNod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005;307(5710):731–4 链接1

[117] Cash HL, Whitham CV, Behrendt CL, Hooper LV. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 2006;313(5790):1126–30 链接1

[118] Molloy MJ, Bouladoux N, Belkaid Y. Intestinal microbiota: shaping local and systemic immune responses. Semin Immunol 2012;24(1):58–66 链接1

[119] Mantis NJ, Rol N, Corthésy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 2011;4(6):603–11 链接1

[120] Palm NW, Rosenstein RK, Medzhitov R. Allergic host defences. Nature 2012;484(7395):465–72 链接1

[121] Macpherson AJ, Harris NL. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 2004;4(6):478–85 链接1

[122] Gaboriau-Routhiau V, Lécuyer E, Cerf-Bensussan N. Role of microbiota in postnatal maturation of intestinal T-cell responses. Curr Opin Gastroenterol 2011;27(6):502–8 链接1

[123] Weiner HL, da Cunha AP, Quintana F, Wu H. Oral tolerance. Immunol Rev 2011;241(1):241–59 链接1

[124] Cassani B, Villablanca EJ, De Calisto J, Wang S, Mora JR. Vitamin A and immune regulation: role of retinoic acid in gut-associated dendritic cell education, immune protection and tolerance. Mol Aspects Med 2012;33(1):63–76 链接1

[125] Hall JA, Grainger JR, Spencer SP, Belkaid Y. The role of retinoic acid in tolerance and immunity. Immunity 2011;35(1):13–22 链接1

[126] Smits HH, van der Vlugt LE, von Mutius E, Hiemstra PS. Childhood allergies and asthma: new insights on environmental exposures and local immunity at the lung barrier. Curr Opin Immunol 2016;42:41–7 链接1

[127] Genuneit J, Strachan DP, Büchele G, Weber J, Loss G, Sozanska B, et alThe combined effects of family size and farm exposure on childhood hay fever and atopy. Pediatr Allergy Immunol 2013;24(3):293–8 链接1

[128] Ege MJ, Herzum I, Büchele G, Krauss-Etschmann S, Lauener RP, Bitter S, et alSpecific IgE to allergens in cord blood is associated with maternal immunity to Toxoplasma gondii and rubella virus. Allergy 2008;63(11):1505–11 链接1

[129] Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, et alFactors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006;118(2):511–21 链接1

[130] Björkstén B. The intrauterine and postnatal environments. J Allergy Clin Immunol 1999;104(6):1119–27 链接1

[131] Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg C, et alDecreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut 2014;63(4):559–66 链接1

[132] Bertrand X, Dufour V, Millon L, Beuvier E, Gbaguidi-Haore H, Piarroux R, et alEffect of cheese consumption on emergence of antimicrobial resistance in the intestinal microflora induced by a short course of amoxicillin-clavulanic acid. J Appl Microbiol 2007;102(4):1052–9.

[133] Mangin I, Lévêque C, Magne F, Suau A, Pochart P. Long-term changes in human colonic Bifidobacterium populations induced by a 5-day oral amoxicillin-clavulanic acid treatment. PLoS One 2012;7(11):e50257 链接1

[134] Stokholm J, Schjørring S, Eskildsen CE, Pedersen L, Bischoff AL, Følsgaard N, et alAntibiotic use during pregnancy alters the commensal vaginal microbiota. Clin Microbiol Infect 2014;20(7):629–35 链接1

[135] Roduit C, Frei R, Loss G, Büchele G, Weber J, Depner M, et alDevelopment of atopic dermatitis according to age of onset and association with early-life exposures. J Allergy Clin Immunol 2012;130(1):130–6.e5 链接1

[136] Sepp E, Julge K, Vasar M, Naaber P, Björksten B, Mikelsaar M. Intestinal microflora of Estonian and Swedish infants. Acta Paediatr 1997; 86 (9):956–61 链接1

[137] Björkstén B, Sepp E, Julge K, Voor T, Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001;108(4):516–20 链接1

[138] Sjögren YM, Jenmalm MC, Böttcher MF, Björkstén B, Sverremark-Ekström E. Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin Exp Allergy 2009;39(4):518–26 链接1

[139] Böttcher MF, Nordin EK, Sandin A, Midtvedt T, Björkstén B. Microflora-associated characteristics in faeces from allergic and nonallergic infants. Clin Exp Allergy 2000;30(11):1591–6 链接1

[140] Kalliomäki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 2001;107(1):129–34 链接1

[141] Björkstén B, Naaber P, Sepp E, Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 1999;29(3):342–6 链接1

[142] Kirjavainen PV, Gibson GR. Healthy gut microflora and allergy: factors influencing development of the microbiota. Ann Med 1999;31(4):288–92 链接1

[143] Böttcher MF, Björkstén B, Gustafson S, Voor T, Jenmalm MC. Endotoxin levels in Estonian and Swedish house dust and atopy in infancy. Clin Exp Allergy 2003;33(3):295–300 链接1

[144] Björkstén B. Environment and infant immunity. Proc Nutr Soc 1999;58(3):729–32 链接1

[145] Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén B, Engstrand L, Jenmalm MC. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 2012;129(2):434–40.e2 链接1

[146] Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy 2014;44(6):842–50 链接1

[147] Bisgaard H, Li N, Bonnelykke K, Chawes BLK, Skov T, Paludan-Müller G, et alReduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 2011;128(3):646–52.e5 链接1

[148] Dicksved J, Flöistrup H, Bergström A, Rosenquist M, Pershagen G, Scheynius A, et alMolecular fingerprinting of the fecal microbiota of children raised according to different lifestyles. Appl Environ Microbiol 2007;73(7):2284–9 链接1

[149] Heederik D, von Mutius E. Does diversity of environmental microbial exposure matter for the occurrence of allergy and asthma? J Allergy Clin Immunol 2012;130(1):44–50 链接1

[150] Lauener RP, Birchler T, Adamski J, Braun-Fahrländer C, Bufe A, Herz U, et alExpression of CD14 and toll-like receptor 2 in farmers’ and non-farmers’ children. Lancet 2002;360(9331):465–6 链接1

[151] Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrländer C, et alToll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol 2004;113(3):482–8 链接1

[152] Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrländer C, et alAssociation between exposure to farming, allergies and genetic variation in CARD4/NOD1. Allergy 2006;61(9):1117–24 链接1

[153] Ege MJ, Bieli C, Frei R, van Strien RT, Riedler J, Ublagger E, et alPrenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J Allergy Clin Immunol 2006;117(4):817–23 链接1

[154] Bieli C, Eder W, Frei R, Braun-Fahrländer C, Klimecki W, Waser M, et alA polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression. J Allergy Clin Immunol 2007;120(6):1308–15 链接1

[155] Loss G, Bitter S, Wohlgensinger J, Frei R, Roduit C, Genuneit J, et alPrenatal and early-life exposures alter expression of innate immunity genes: the PASTURE cohort study. J Allergy Clin Immunol 2012;130(2):523–30.e9 链接1

[156] Roduit C, Wohlgensinger J, Frei R, Bitter S, Bieli C, Loeliger S, et alPrenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis. J Allergy Clin Immunol 2011;127(1):179–85.e1 链接1

[157] Orivuori L, Loss G, Roduit C, Dalphin JC, Depner M, Genuneit J, et alSoluble immunoglobulin A in breast milk is inversely associated with atopic dermatitis at early age: the PASTURE cohort study. Clin Exp Allergy 2014;44(1):102–12 链接1

[158] Karlsson H, Hessle C, Rudin A. Innate immune responses of human neonatal cells to bacteria from the normal gastrointestinal flora. Infect Immun 2002;70(12):6688–96 链接1

[159] Lundell AC, Andersson K, Josefsson E, Steinkasserer A, Rudin A. Soluble CD14 and CD83 from human neonatal antigen-presenting cells are inducible by commensal bacteria and suppress allergen-induced human neonatal Th2 differentiation. Infect Immun 2007;75(8):4097–104 链接1

[160] Kääriö H, Huttunen K, Karvonen AM, Schaub B, von Mutius E, Pekkanen J, et alExposure to a farm environment is associated with T helper 1 and regulatory cytokines at age 4.5 years. Clin Exp Allergy 2016;46(1):71–7 链接1

[161] Kääriö H, Nieminen JK, Karvonen AM, Huttunen K, Schröder PC, Vaarala O, et alCirculating dendritic cells, farm exposure and asthma at early age. Scand J Immunol 2016;83(1):18–25 链接1

[162] Martikainen MV, Kääriö H, Karvonen A, Schröder PC, Renz H, Kaulek V, et alFarm exposures are associated with lower percentage of circulating myeloid dendritic cell subtype 2 at age 6. Allergy 2015;70(10):1278–87 链接1

[163] Roduit C, Frei R, Depner M, Schaub B, Loss G, Genuneit J, et alIncreased food diversity in the first year of life is inversely associated with allergic diseases. J Allergy Clin Immunol 2014;133(4):1056–64.e7 链接1

[164] Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001;357(9262):1076–9 链接1

[165] Zuccotti G, Meneghin F, Aceti A, Barone G, Callegari ML, Di Mauro A, et alProbiotics for prevention of atopic diseases in infants: systematic review and meta-analysis. Allergy 2015;70(11):1356–71 链接1

[166] Cuello-Garcia CA, Brożek JL, Fiocchi A, Pawankar R, Yepes-Nuñez JJ, Terracciano L, et alProbiotics for the prevention of allergy: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol 2015;136(4):952–61 链接1

[167] Zhang G, Hu H, Liu C, Zhang Q, Shakya S, Li Z. Probiotics for prevention of atopy and food hypersensitivity in early childhood: a PRISMA-compliant systematic review and meta-analysis of randomized controlled trials. Medicine 2016;95(8):e2562 链接1

[168] Koletzko S. Probiotics and prebiotics for prevention of food allergy: indications and recommendations by societies and institutions. J Pediatr Gastroenterol Nutr 2016;63(Suppl 1):S9–10.

[169] Gorelik L, Kauth M, Gehlhar K, Bufe A, Holst O, Peters M. Modulation of dendritic cell function by cowshed dust extract. Innate Immun 2008;14(6):345–55 链接1

[170] Stiehm M, Bufe A, Peters M. Proteolytic activity in cowshed dust extracts induces C5a release in murine bronchoalveolar lavage fluids which may account for its protective properties in allergic airway inflammation. Thorax 2013;68(1):31–8 链接1

[171] Peters M, Kauth M, Scherner O, Gehlhar K, Steffen I, Wentker P, et alArabinogalactan isolated from cowshed dust extract protects mice from allergic airway inflammation and sensitization. J Allergy Clin Immunol 2010;126(3):648–56.e4 链接1

[172] Kepert I, Fonseca J, Müller C, Milger K, Hochwind K, Kostric M, et alD-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease. J Allergy Clin Immunol. Epub 2016 Sep 23 链接1

[173] Kauth M, Heine H. Allergy protection by cowshed bacteria—recent findings and future prospects. Pediatr Allergy Immunol 2016;27(4):340–7 链接1

[174] Vogel K, Blümer N, Korthals M, Mittelstädt J, Garn H, Ege M, et alAnimal shed Bacillus licheniformis spores possess allergy-protective as well as inflammatory properties. J Allergy Clin Immunol 2008;122(2):307–12.e8 链接1

[175] Debarry J, Garn H, Hanuszkiewicz A, Dickgreber N, Blümer N, von Mutius E, et alAcinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties. J Allergy Clin Immunol 2007;119(6):1514–21 链接1

[176] Debarry J, Hanuszkiewicz A, Stein K, Holst O, Heine H. The allergy-protective properties of Acinetobacter lwoffii F78 are imparted by its lipopolysaccharide. Allergy 2010;65(6):690–7 链接1

[177] Stein K, Brand S, Jenckel A, Sigmund A, Chen ZJ, Kirschning CJ, et alEndosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects. J Allergy Clin Immunol 2017;139(2):667–78.e5 链接1

[178] Fischer K, Stein K, Ulmer AJ, Lindner B, Heine H, Holst O. Cytokine-inducing lipoteichoic acids of the allergy-protective bacterium Lactococcus lactis G121 do not activate via Toll-like receptor 2. Glycobiology 2011;21(12):1588–95 链接1

[179] Conrad ML, Ferstl R, Teich R, Brand S, Blümer N, Yildirim AO, et alMaternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J Exp Med 2009;206(13):2869–77 链接1

[180] Brand S, Teich R, Dicke T, Harb H, Yildirim AÖ, Tost J, et alEpigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes. J Allergy Clin Immunol 2011;128(3):618–25.e7 链接1

[181] Hagner S, Harb H, Zhao M, Stein K, Holst O, Ege MJ, et alFarm-derived Gram-positive bacterium Staphylococcus sciuri W620 prevents asthma phenotype in HDM- and OVA-exposed mice. Allergy 2013;68(3):322–9 链接1