**10. References**

378 Atopic Dermatitis – Disease Etiology and Clinical Management

Better understanding of the effects of different probiotic strains and a deeper insight into the mechanisms of the heterogeneous manifestations of AD are needed for the validation of specific strains carrying anti-allergic potential. Therefore, research activities are currently focusing on identification of specific probiotic strains with immunomodulatory potential and on how dietary content interacts with the most efficacious probiotic strains. Moreover, the selection of the most beneficial probiotic strain, the dose, and the timing of supplementation still need to be determined. Further studies should also clarify if any susceptible groups of AD exist and how these groups benefit from supplementation with

Some studies in the management of AD suggest that therapeutic benefit requires a combination of probiotic species (as with VSL#3 or Lacto-mix) or that the component(s) responsible for the anti-inflammatory effect in combination preparations have specific properties that monotherapy probiotics do not [112]. This concept also supports the use of prebiotics that increase concentrations of several commensal immunoregulatory bacteria. Prebiotic use was shown to be associated with a reduction in the faecal concentration of Bacteroides fragilis, but had no effect on Lactobacilli or Bifidobacteria. Genetically modified probiotics will be tested for their ability to attenuate AD thru secreting regulatory cytokines in experimental models as well [113]. In near future, the researchers will look for more appropriate combinations of probiotic species or modified probiotics with/without prebiotic

Additionally, side effects are very low and they might not be nonexistent, as shown in a set of patients with different diseases. However, probiotics should not be considered as totally harmless, particularly in the immunodeficient host, and more safety studies are needed. As imagined, probiotics may have unpredictable behaviour like all microorganisms, such as unanticipated gene expression in nonnative host environment, or acquired mutations occurring spontaneously via bacterial DNA-transfer mechanisms [114]. And certain probiotics are known to stimulate Th1 immunity, which has been suggested as one of the

Since conclusions on probiotics are limited to specific strains and models, they should

 Probiotics should not be considered as completely harmless, particularly in the immunodeficient host, and more safety studies are needed [100-110, 115,116]. Physiological use (normal route, normal dose, normal growth phase, specific strain or substrain/species) is studied in all cases, so as not to overwhelm (high dose) or

 Do probiotics really induce/exacerbate Th1 and / or Th2- mediated diseases? Such as being reported an increased rate of recurrent wheezing episodes, an augmented rate of atopic disorders, increased sensitization to allergens as well as autoimmune disorders. Lactobacilli and Bifidobacteria have specific dose- and duration- dependent

immunomodulatory effects on the proliferation of B-/T-lymphocytes [108-110]. The researchers ought to look for more appropriate and safe combinations of probiotic species (as with VSL#3 or Lacto-mix) or modified probiotics with/without prebiotic

 Research activities are currently focusing on identification of specific probiotic strains with immunomodulatory potential and on how dietary content interacts with the most

mechanisms by which they can suppress Th2-mediated allergic diseases [110].

certain probiotic strains.

**9. Key issues**

not be generalized [20,35].

and test them in human/experimental AD models.

circumvent natural immune processing [100-110].

and test them in human/experimental AD models [112].

The Role of Probiotics in Atopic Dermatitis Prevention and Therapy 381

[32] Pessi T, Isolauri E, Sutas Y, Kankaanranta H, Moilanen E, Hurme M. Suppression of T

[33] Kaila M, Isolauri E, Soppi E, Virtanen E, Laine S, Arvilommi H. Enhancement of the

[34] Ruemmele FM, Bier D, Marteau P, Rechkemmer G, Bourdet-Sicard R, Walker WA,

[35] Christensen HR, Frokiaer H, Pestka JJ. Lactobacilli differentially modulate expression of

[36] Salminen SJ, Gueimonde M, Isolauri E. Probiotics that modify disease risk. J Nutr 2005;

[37] Niers LE, Timmerman HM, Rijkers GT et al. Identification of strong interleukin–10

[38] Maassen CB, van Holten-Neelen C, Balk F, den Bak-Glashouwer MJ, Leer RJ, Laman JD,

[40] West CE, Hammarström ML, Hernell O. Probiotics during weaning reduce the

[41] Sistek D, Kelly R, Wickens K, Stanley T, Fitzharris P, Crane J. Is the effect of probiotics

[42] Kim JY, Choi YO, Ji GE. Effect of oral probiotics (Bifidobacterium lactis AD011 and

[43] Takahashi N, Kitazawa H, Iwabuchi N, Xiao JZ, Miyaji K, Iwatsuki K, Saito T.

[44] Shida K, Makino K, Morishita A. Lactobacillus casei inhibits antigen induced IgE

[45] Thomas DJ, Husmann RJ, Villamar M, Winship TR, Buck RH, Zuckermann FA.

[46] Rosenfeldt V, Benfeldt E, Nielsen SD, Michaelsen KF, Jeppesen DL, Valerius NH,

incidence of eczema. Pediatr Allergy Immunol. 2009;20(5):430-7.

allergy mouse model. J Microbiol Biotechnol 2008; 18: 1393-1400.

by orally administered Lactobacillus strains. Vaccine 2000; 18: 2613–23. [39] Kruisselbrink A, Heijne Den Bak-Glashouwer MJ, Havenith CE, Thole JE, Janssen R.

Immunopharmacology 2001; 1: 211–8.

Lactobacillus strain. Pediatr Res 1992; 32: 141–4.

Pediatr Gastroenterol Nutr 2009; 48: 126-41.

responses. Clin Exp Immunol 2001; 126: 2–8.

Int Arch Allergy Immunol 1998;115:278-87.

dermatitis. J Allergy Clin Immunol 2003; 111: 389-95.

PLoS One. 2011; 6(2): e16577.

2002; 168: 171–8.

Exp Allergy 2005; 35: 1481–9.

135: 1294-8.

36: 629-33.

145:130-8.

cell activation by Lactobacillus rhamnosus GG-degraded bovine casein.

circulating antibody secreting cell response in human diarrhea by a human

Goulet O. Clinical evidence for immunomodulatory effects of probiotic bacteria. J

cytokines and maturation surface markers in murine dendritic cells. J Immunol

inducing lactic acid bacteria which downregulate T helper type 2 cytokines. Clin

Boersma WJ, Claassen E. Strain-dependent induction of cytokine profiles in the gut

Recombinant Lactobacillus plantarum inhibits house dust mite-specific T-cell

on atopic dermatitis confined to food sensitized children? Clin Exp Allergy 2006;

Lactobacillus acidophilus AD031) administration on ovalbumin-induced food

Immunostimulatory oligodeoxynucleotide from Bifidobacterium longum suppresses Th2 immune responses in a murine model. Clin Exp Immunol 2006;

secretion through regulation of cytokine production in murine splenocyte cultures.

Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model.

Paerregaard A. Effect of probiotic Lactobacillus strains in children with atopic

[16] Kalliomäki M, Salminen S, Poussa T, Isolauri E. Probiotics during the first 7 years of life:

[17] Darsow U, Wollenberg A, Simon D, Taïeb A, Werfel T, Oranje A, et al. ETFADEADV

[18] Colin R Simpson, John Newton, Julia Hippisley-Cox, Aziz Sheikh. Trends in the

[19] Bongaerts GP, Severijnen RS. Preventive and curative effects of probiotics in atopic

[20] Walker WA. Mechanisms of action of probiotics. Clin Infect Dis 2008; 46 Suppl 2:S87-91;

[21] 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. [22] Watanabe S, Narisawa Y, Arase S, Okamatsu H, Ikenaga T, Tajiri Y, Kumemura M.

[23] Kirjavainen PV, Arvola T, Salminen SJ, Isolauri E. Aberrant composition of gut

[24] Sepp E, Julge K, Mikelsaar M, Björkstén B. Intestinal microbiota and immunoglobulin E responses in 5-year-old Estonian children. Clin Exp Allergy 2005, 35(9): 1141-6. [25] Adlerberth I, Strachan DP, Matricardi PM, Ahrné S, Orfei L, Aberg N, et al. Gut

[26] Penders J, Stobberingh EE, Thijs C, Adams H, Vink C, van Ree R, van den Brandt PA et

eczema was or was not developing. Clin Exp Allergy 2006, 36(12): 1602-8. [27] Sudo N, Sawamura S, Tanaka K, Aiba Y, Kubo C, Koga Y. The requirement of intestinal

[28] Viljanen M, Kuitunen M, Haahtela T, Juntunen-Backman K, Korpela R, Savilahti E.

[29] Isolauri E. Studies on Lactobacillus GG in food hypersensitivity disorders. Nutr Today

[30] Cebra JJ. Influences of microbiota on intestinal immune system development. Am J Clin

[31] Malin MV, Korhonen H, Syvaoja EL, et al. Dietary therapy with lactobacillus GG,

control subjects. J Allergy Clin Immunol 2005, 111(3): 587-91.

Allergy Clin Immunol 2007, 119(4):1019-21.

2009: 102: 108–117. doi: 10.1258/jrsm.2009.080211.

patients. Med Hypotheses. 2005;64(6):1089-92.

Allergy Clin Immunol 2007, 120(2): 343-50.

oral tolerance induction. J Immunol 1997; 159: 1739–45.

3083.2009.03415.x

discussion S144-51.

2002; 51–55.

Suppl 1996; 31: 285–315.

1997; 5: 219-36.

Nutr 1999; 69: 1046S–1051S.

a cumulative risk reduction of eczema in a randomized, placebo- controlled trial. J

eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol. 2010; 24(3): 317-28. doi: 10.1111/j.1468-

epidemiology and prescribing of medication for eczema in England. J R Soc Med

Differences in fecal microflora between patients with atopic dermatitis and healthy

microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Gut

microbiota and development of atopic eczema in 3 European birth cohorts. J

al. Molecular finger printing of the intestinal microbiota of infants in whom atopic

bacterial flora for the development of an IgE production system fully susceptible to

Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants. Pediatr Allergy Immunol 2005; 16: 65-71.

bovine colostrum or bovine immune colostrum in patients with juvenile chronic arthritis: evaluation of effect on gut defense mechanisms. Inflammopharmacology

The Role of Probiotics in Atopic Dermatitis Prevention and Therapy 383

[61] Smits HH, Engering A, van der Kleij D et al. Selective probiotic bacteria induce IL-10-

[62] Kim JY, Choi YO, Ji GE. Effect of oral probiotics (Bifidobacterium lactis AD011 and

[63] Feleszko W, Jaworska J, Rha RD et al. Probiotic-induced suppression of allergic

[64] Fujimura T, Okuyama R, Ito Y, Aiba S. Profiles of Foxp3+ regulatory T cells in

[65] Kwon HK, Lee CG, So JS, Chae CS, Hwang JS, Sahoo A, et al. Generation of regulatory

[66] Hacini-Rachinel F, Gheit H, Le Luduec JB, Dif F, Nancey S, Kaiserlian D. Oral probiotic

[67] Taylor AL, Hale J, Hales BJ, Dunstan JA, Thomas WR, Prescott SL. FOXP3 mRNA

[68] Gerasimov SV, Vasjuta VV, Myhovych OO, Bondarchuk LI. Probiotic supplement

[69] Roessler A, Friedrich U, Vogelsang H, Bauer A, Kaatz M, Hipler UC, Schmidt I, Jahreis

[70] Hoarau C, Lagaraine C, Martin L, Velge-Roussel F, Lebranchu Y. Supernatant of

[71] Forsythe P, Inman MD, Bienenstock J. Oral treatment with live Lactobacillus reuteri

[72] Viljanen M, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure

allergy mouse model.J Microbiol Biotechnol. 2008;18(8):1393-400.

immune disorders. Proc Natl Acad Sci USA 2010; 107(5): 2159-64.

1618–25.

2007; 37: 498-505.

2008; 158(6): 1256-63.

One. 2009; 4(3): e4903.

10.2165/11531420-000000000-00000.

18(1): 10-9.

93-102.

2007;175(6):561-9.

Allergy Clin Immunol 2005; 115: 1260–7.

CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr 2004; 80:

producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J

Lactobacillus acidophilus AD031) administration on ovalbumin-induced food

sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy

eczematous dermatitis, psoriasis vulgaris and mycosis fungoides. Br J Dermatol.

dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses

control skin inflammation by acting on both effector and regulatory T cells. PLoS

expression at 6 months of age is higher in infants who develop atopic dermatitis, but is not affected by giving probiotics from birth. Pediatr Allergy Immunol 2007,

reduces atopic dermatitis in preschool children: a randomized, double-blind, placebo-controlled, clinical trial. Am J Clin Dermatol. 2010; 11(5): 351-61. doi:

G. The immune system in healthy adults and patients with atopic dermatitis seems to be affected differently by a probiotic intervention. Clin Exp Allergy. 2008; 38(1):

Bifidobacterium breve induces dendritic cell maturation, activation, and survival through a Toll-like receptor 2 pathway. J Allergy Clin Immunol 2006; 117: 696–702.

inhibits the allergic airway response in mice. Am J Respir Crit Care Med.

T, Kuitunen M. Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Allergy. 2005; 60(4): 494-500. [73] Kukkonen K, Savilahti E, Haahtela T, et al. Probiotics and prebiotic

galactooligosaccharides in the prevention of allergic diseases: a randomized, doubleblind, placebo-controlled trial. J Allergy Clin Immunol. 2007; 119(1): 192–8.

[47] Brouwer ML, Wolt-Plompen SA, Dubois AE, van der Heide S, Jansen DF, Hoijer MA,

a randomized placebo-controlled trial. Clin Exp Allergy. 2006; 36(7): 899-906. [48] Pohjavuori E, Viljanen M, Korpela R, Kuitunen M, Tiittanen M, Vaarala O, Savilahti

[49] Prescott SL, Dunstan JA, Hale J, Breckler L, Lehmann H, Weston S, Richmond P.

[50] Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S. Probiotics in the management of

[51] Boyle RJ, Ismail IH, Kivivuori S, Licciardi PV, Robins-Browne RM, Mah LJ, et al.

[52] Böttcher MF, Abrahamsson TR, Fredriksson M, Jakobsson T, Björkstén B.Low breast

[53] Betsi GI, Papadavid E, Falagas ME. Probiotics for the treatment or prevention of atopic

[54] Chiba Y, Shida K, Nagata S, Wada M, Bian L, Wang C, et al. Well-controlled

[55] Lavasani S, Dzhambazov B, Nouri M, Fåk F, Buske S, Molin G, Thorlacius H, Alenfall J,

[56] Woo SI, Kim JY, Lee YJ, Kim NS, Hahn YS. Effect of Lactobacillus sakei

[57] Marschan E, Kuitunen M, Kukkonen K, Poussa T, Sarnesto A, Haahtela T, Korpela R,

[58] Niers LE, Hoekstra MO, Timmerman HM, van Uden NO, de Graaf PM, Smits HH,

[59] Hart AL, Lammers K, Brigidi P et al. Modulation of human dendritic cell phenotype

[60] Braat H, van den Brande J, van Tol E, Hommes D, Peppelenbosch M, van Deventer S.

and function by probiotic bacteria. Gut 2004; 53: 1602–9.

cow's milk allergy. J Allergy Clin Immunol. 2004; 114(1): 131-6.

atopic eczema. Clin Exp Allergy. 2000; 30(11):1604-10.

Lactobacillus casei. Immunology. 2010; 130(3):352-62.

regulatory T cells. PLoS One. 2010; 5(2): e9009.

Asthma Immunol. 2010; 104(4): 343-8.

35(12): 1557-64.

9995.2010.02507.x.

2008;19(6):497-504.

611-8.

149: 344-52.

Dermatol 2008; 9: 93-103.

Kauffman HF, Duiverman EJ. No effects of probiotics on atopic dermatitis in infancy:

E.Lactobacillus GG effect in increasing IFN-gamma production in infants with

Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis. Clin Exp Allergy. 2005;

Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy. 2011;66(4):509-16. doi: 10.1111/j.1398-

milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy. Pediatr Allergy Immunol.

dermatitis: a review of the evidence from randomized controlled trials. Am J Clin

proinflammatory cytokine responses of Peyer's patch cells to probiotic

Jeppsson B, Weström B. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing

supplementation in children with atopic eczema-dermatitis syndrome.Ann Allergy

Savilahti E, Vaarala O. Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation. Clin Exp Allergy. 2008; 38(4):

Kimpen JL, Rijkers GT. Selection of probiotic bacteria for prevention of allergic diseases: immunomodulation of neonatal dendritic cells. Clin Exp Immunol 2007;

Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated

CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr 2004; 80: 1618–25.

The Role of Probiotics in Atopic Dermatitis Prevention and Therapy 385

[88] Kopp MV, Isabell Hennemuth, Andrea Heinzmann, Radvan Urbanek. Randomized,

[90] Fölster-Holst R, Müller F, Schnopp N, Abeck D, Kreiselmaier I, Lenz T, von Rüden U, et

[92] Zhu DL, Yang WX, Yang HM. [Meta analysis of lactic acid bacteria as probiotics for the

[93] Osborn DA, Sinn JK. Probiotics in infants for prevention of allergic disease and food

[94] Michail S, Onady G, Stolfi A, Johnson T. Efficacy of probiotics in treatment of

[95] Lee J, Seto D, Bielory L. Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. J Allergy Clin Immunol 2008; 121:116-21. [96] Boyle RJ, Bath-Hextall FJ, Leonardi-Bee J, Murrell DF, Tang ML. Probiotics for treating

[97] Williams HC, Grindlay DJ. What's new in atopic eczema? An analysis of systematic

[98] Ogden NS, Bielory L. Probiotics. A complementary approach in the treatment and

[99] Batchelor JM, Grindlay DJ, Williams HC. What's new in atopic eczema? An analysis of

[100]Ishibashi N, Yamazaki S. Probiotics and safety. Am J Clin Nutr. 2001; 73(Suppl):

[101] Kunz AN, Noel JM, Fairchok MP. Two cases of Lactobacillus bacteremia during probiotic treatment of short gut syndrome. J Pediatr Gastroenterol Nutr 2004; 38: 457-8. [102] Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK. Lactobacillus sepsis associated with probiotic therapy. Pediatrics. 2005; 115(1): 178-81. [103] Thompson C, McCarter YS, Krause PJ, Herson VC. Lactobacillus acidophilus sepsis in

[104] Broughton RA, Gruber WC, Haffar AA, Baker CJ. Neonatal meningitis due to

[105] Maassen CB, Claassen E. Strain-dependent effects of probiotic lactobacilli on EAE

hypersensitivity. Cochrane Database Syst Rev 2007; 4:CD006475.

eczema. Cochrane Database Syst Rev. 2008; (4): CD006135.

7; quiz 827-8. doi: 10.1111/j.1365-2230.2010.03901.x.

a neonate. J Perinatol. 2001; 21(4):258-60.

autoimmunity.Vaccine. 2008; 26(17): 2056-7.

Lactobacillus. Pediatr Infect Dis. 1983; 2(5): 382–4.

of atopic dermatitis in infancy. Allergy 2007; 62(11): 1270-6.

Clin Exp Allergy 2009; 39: 571-8.

Exp Dermatol. 2010; 35(3): 223-7.

12(9): 734-9.

101(5): 508-16.

5(2):179-84.

465S– 470S.

double-blind, placebo-controlled trial of probiotics for primary prevention: No clinical effects of Lactobacillus GG supplementation. Pediatrics 2008; 121: e850-6. [89] Grüber C, Wendt M, Sulser C, Lau S, Kulig M, Wahn U, Werfel T, Niggemann B.

Randomized, placebo-controlled trial of Lactobacillus rhamnosus GG as treatment

al. Prospective, randomized controlled trial on Lactobacillus rhamnosus in infants with moderate to severe atopic dermatitis. Br J Dermatol 2006, 155(6): 1256-61. [91] Soh SE, Aw M, Gerez I, et al. Probiotic supplementation in the first 6 months of life in at

risk Asian infants--effects on eczema and atopic sensitization at the age of 1 year.

primary prevention of infantile eczema]. Zhongguo Dang Dai Er Ke Za Zhi. 2010;

pediatric atopic dermatitis a meta-analysis of randomized, controlled trials. 2008,

reviews published in 2007 and 2008. Part 2. Disease prevention and treatment. Clin

prevention of pediatric atopic disease. Curr Opin Allergy Clin Immunol 2005,

systematic reviews published in 2008 and 2009. Clin Exp Dermatol. 2010; 35(8): 823-

[74] Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T,

[75] Abrahamsson TR, Jakobsson T, Bottcher MF, et al. Probiotics in prevention of IgE-

[76] Isolauri E, Rautava S, Kalliomäki M, Kirjavainen P, Salminen S. Role of probiotics in food hypersensitivity. Curr Opin Allergy Clin Immunol 2002; 2: 263-71. [77] Kirjavainen PV, Salminen SJ, Isolauri E. Probiotic bacteria in the management of atopic

[78] Weston S, Halbert A, Richmond P, Prescott SL. Effects of probiotics on atopic dermatitis. A randomised controlled trial. Arch Dis Child 2005, 90(9): 892-7. [79] Hoang BX, Shaw G, Pham P, Levine SA. Lactobacillus rhamnosus cell lysate in the

[80] Hattori K, Yamamoto A, Sasai M, Taniuchi S, Kojima T, KobayashiY, et al. Effects of

[81] Wickens K, Black PN, Stanley TV, et al. A differential effect of 2 probiotics in the

[82] Niers L, Martín R, Rijkers G, Sengers F, Timmerman H, van Uden N, et al. The effects of

[83] Kim JY, Kwon JH, Ahn SH, Lee SI, Han YS, Choi YO, et al. Effect of probiotic mix

[84] Dotterud CK, Storrø O, Johnsen R, Oien T. Probiotics in pregnant women to prevent

[85] Lodinova-Zadnikova R, Cukrowska B, Tlaskalova-Hogenova H. Oral administration of

[86] Huurre A, Laitinen K, Rautava S, Korkeamäki M, Isolauri E. Impact of maternal atopy

blind placebo-controlled study. Clin Exp Allergy. 2008; 38(8):1342-8. [87] Taylor A, Dunstan J, Prescott S. Probiotic supplementation for the first 6 months of life

infants with atopic dermatitis. Arerugi 2003; 52: 20–30.

trial. Pediatr Allergy Immunol. 2010; 21(2 Pt 2): e386-93.

trial. J Allergy Clin Immunol 2008; 122: 788-94.

23. doi: 10.1111/j.1365-2133.2010.09889.x.

Allergy. 2009; 64(9): 1349-58.

2009; 123: 335-41.

2003; 36(2): 223-7.

2010; 9(3): 192-6.

131(3): 209-11.

Immunol 2007; 119:184-91.

Clin Immunol. 2007; 119(5): 1174–1180.

Haahtela T, Savilahti E. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol

associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy

disease: underscoring the importance of viability. J Pediatr Gastroenterol Nutr.

management of resistant childhood atopic eczema. Inflamm Allergy Drug Targets.

administration of bifidobacteria on fecal microflora and clinical symptoms in

prevention of eczema and atopy: a double-blind, randomized, placebo-controlled

selected probiotic strains on the development of eczema (the PandA study).

(Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind, randomized, placebo-controlled

allergic disease: a randomized, double-blind trial. Br J Dermatol. 2010; 163(3): 616-

probiotic Escherichia coli after birth reduces frequency of allergies and repeated infections later in life (after 10 and 20 years). Int Arch Allergy Immunol 2003,

and probiotic supplementation during pregnancy on infant sensitization: a double-

fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin

**22**

*USA*

**Food Compounds Inhibit** *Staphylococcus*

Enterotoxigenic *S. aureus* is a major bacterial pathogen that develops multi-drug resistance to antibiotics (Pereira et al., 2009; Pu et al., 2011; Rhee & Woo, 2010). The enterotoxigenic bacteria and secreted toxins have been reported to cause clinical infections, and it has also been reported that they contaminate a broad variety of foods, including breaded chicken products (Pepe et al., 2006), canned mushrooms (Anderson et al., 1996), cheeses (Ertas et al., 2010; Ostyn et al., 2010; Rosengren et al., 2010), raw milk (Fusco et al., 2011; Heidinger et al., 2009), pork meat (Wallin-Carlquist et al., 2010), and other foods (Balaban & Rasooly, 2000) as well contaminating handles of shopping carts (Mizumachi et al., 2011) causing many foodborne illnesses in the United States each year (Shinefield & Ruff, 2009). Staphylococcal food poisoning is due to the absorption from the digestive tract into the circulation of the enterotoxins preformed in food A toxin level of <1 µg may induce symptoms of food poisoning. This level is reached with a bacterial population of >105

*S. aureus* produces the virulent staphylococcal enterotoxin A (SEA), a single chain protein that consists of 233 amino acid residues with a molecular weight of 27,078 Da. It has been estimated that staphylococcal enterotoxin A (SEA) secreted by the bacteria is associated with 78% of staphylococcal outbreaks (Vernozy-Rozand et al., 2004). Heat used to eliminate the pathogenic bacteria may not eliminate toxins already formed (Margosch et al., 2005; Pepe et al., 2006). Staphylococcus enterotoxins (SEs) exhibit two separate biological activities: they cause gastroenteritis in the gastrointestinal tract and they act as a superantigen on the immune system. Previous research has shown that emetic activities and superantigenic activities of

Because SEA is present in contaminated foods and exerts adverse effects on the gastrointestinal tract, there is a need to find food-compatible safe conditions to inactivate it. Efforts to inhibit the toxin or its release from *S. aureus* include the use of electrolyzed water (Suzuki et al., 2002), high pressure and heat (Margosch et al., 2005), radiation and pulsed electric fields (Walkling-Ribeiro et al., 2008), condensed tannins (Choi et al., 2007) and other plant extracts (Carlos et al., 2010; Ifesan & Voravuthlkunchai, 2009), peptides (Wang et al.,

**1. Introduction**

CFU/g food (Stewart, 2005).

SEs are related (Shinefield & Ruff, 2009; Stewart, 2005).

*Aureus* **Bacteria and the Toxicity of**

**Associated with Atopic Dermatitis**

*Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, California*

Reuven Rasooly and Mendel Friedman

**Staphylococcus Enterotoxin A (SEA)**