A clinical reading on “World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics”

Abstract

This article was originally published online on 10 March 2016 Since the immunomodulatory properties of probiotics have been described, the effect of probiotic supplementation has been investigated in several trials and it has been also proposed as a preventive intervention for the development of allergic diseases. Recently two important evidence-based recommendations about the use of probiotics in the prevention of allergy were published [1.Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8:4.Google Scholar, 2.Muraro A. Halken S. Arshad S.H. Beyer K. Dubois A.EJ. Du Toit G. et al.EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy.Allergy. 2014; 69: 590-601Crossref PubMed Scopus (345) Google Scholar] with conflicting conclusions, in particular the most recent guideline [1.Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8:4.Google Scholar] seems to be partially in contradiction with the previous statements about prevention of eczema. For these reasons, we tried to analyze the evidences leading to these recommendations [1.Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8:4.Google Scholar] to highlight the aspects that can be more directly related or correlated with clinical practice. This clinical reading was addressed to offer some reflections about the methods used to formulate such recommendations, and the possibility to adopt in the clinical practice the proposed conclusions. We tried to retraces the path proposed by the Authors to analyse three important questions about the efficacy of probiotics in preventing allergic diseases if administrated to pregnant women (first question), to breastfeeding mothers (second question) and in healthy infants (third question). These questions have been investigated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach [3.GRADE Working GroupGrading quality of evidence and strength of recommendations.BMJ. 2004; 328: 1490-1494Crossref PubMed Google Scholar], to perform a systematic review of randomized controlled trials and formulate recommendations. In summary, the GRADE method aims to define a rigorous and explicit method for the production of clinical recommendations. According to this method, the knowledge of advantages and disadvantages, benefits and risks of an intervention is necessary to make decisions in the health field. The GRADE approach also provides a three-phases decisional framework: a) formulation of a clinical question, with the choice and the formal evaluation of its related outcomes, and systematic evaluation of the scientific literature and the quality of the evidence; b) evaluation of the benefits and risks associated to the intervention, taking also in consideration its feasibility, the necessary resources and the patients’ preferences; c) formal definition of the strength of the recommendation. From a methodological point of view, it should be noted that the recommendations are directed to patients, clinicians and other health care professionals with different objectives, as clearly explained in the guidelines introduction. Each recommendation can have different levels of strength: strong recommendation indicates that patients would like to receive the intervention and that clinicians should actuate it. Conditional or weak recommendation indicates that the majority of patients would like to receive the intervention, but many other not, as well as they hope that clinicians would recognize that different choices may be appropriate for different patients, by taking advantage of decision-making tools to help patients to make consistent choices. In the results section of the guidelines we can read that “Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the World Allergy Organization (WAO) guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema” [1.Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8:4.Google Scholar]. In the first sentence, the guideline panel confirmed the absence of evidence of effectiveness in the use of probiotics in the primary prevention of the common allergic diseases (asthma, food allergy, rhinitis). The second sentence deserves a careful review, because it seems to contradict the meaning of the first sentence and the position of the other guidelines, including the recent European Academy of Allergy and Clinical Immunology (EAACI) guideline [2.Muraro A. Halken S. Arshad S.H. Beyer K. Dubois A.EJ. Du Toit G. et al.EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy.Allergy. 2014; 69: 590-601Crossref PubMed Scopus (345) Google Scholar]. In order to comment this phrase, we started from the description of the evidences (GRADE) in Appendix 2 - Question 1: “Should probiotics vs. no probiotics be used in pregnant women?” In this appendix we can found declared how many studies addressing this question have been selected for each of the clinical objectives: 15 randomized trials were considered for the prevention of eczema. The comment of this question can be also reliable if it is applied to the other two questions above, as approximately the same studies have been selected for critical review. In this regard, we carefully examined the individual trials to better analyze and understand the results of the question. The most important clinical features that supported our considerations are reported in Table 1 and Table 2.Table 1Characteristics of the 15 trials included in the meta-analysis and addressing the guideline’s Question 1: “Should probiotics vs. no probiotics be used in pregnant women?”.ReferencesPopulation at risk of atopyN° patientsProbioticDuration of ante-partum therapyDuration of therapy in breastfed infantsDuration of therapy in infants fed with formulasKalliomaki et al. 2001 [4.Kalliomaki 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;357:1076–9.Google Scholar]yes159Lactobacillus rhamnosus GG (ATCC 55103)2-4 weeks6 months6 monthsRautava et al. 2002 [5.Rautava S. Kalliomaki M. Isolauri E. Probiotics during pregnancy and breastfeeding might confer immunomodulatory protection against atopic disease in the infant.J Allergy Clin Immunol. 2002; 109: 119-121Abstract Full Text Full Text PDF PubMed Scopus (484) Google Scholar]aAnalysis of a subgroup of patients previous analyzed by Kalliomaki et al. [4]yes62Lactobacillus rhamnosus GG (ATCC 53103)4 weeks3 months3 monthsAbrahamsson et al. 2007 [6.Abrahamsson TR, Jakobsson T, Bottcher MF, Fredrikson M, Jenmalm MC, Bjorksten B, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119:1174–80.Google Scholar]yes232Lactobacillus reuteri (ATCC55730)4 weeks12 months12 monthsKukkonen et al. 2007 [7.Kukkonen K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar]yes1223Lactobacillus rhamnosus GG (ATCC 55103), Lactobacillus rhamnosus LC705 (DSM7061), Bifidobacterium breve Bb99 (DSM13692), Propionibacterium freudenreichiii ssp shermanii JS (DSM7076)2-4 weeks6 months6 monthsHuurre et al. 2008 [8.Huurre A, Laitinen K, Rautava S, Korkeamäki M, Isolauri E. Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: A double-blind placebo-controlled study. Clin Exp Allergy. 2008;38:1342–8.Google Scholar]yes171Lactobacillus rhamnosus GG (ATCC 55103) Bifidobacterium lactis Bb126 monthsend of breastfeeding-Marschan et al. 2008 [9.Marschan E. Kuitunen M. Kukkonen K. Poussa T. Sarnesto A. Haahtela T. et al.Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.Clin Exp Allergy. 2008; 38: 611-618Crossref PubMed Scopus (144) Google Scholar]bAnalysis of a subgroup of patients previous analyzed by Kukkonen et al. [7]yes98Lactobacillus rhamnosus GG (ATCC 55103), Lactobacillus rhamnosus LC705 (DSM7061), Bifidobacterium breve Bb99 (DSM13692), Propionibacterium freudenreichiii ssp shermanii JS (DSM7076)2-4 weeks6 months6 monthsWickens et al. 2008 [10.Wickens K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google rhamnosus Bifidobacterium lactis weeks6 et al. 2008 A. R. placebo-controlled of probiotics for primary no clinical of Lactobacillus GG 2008; PubMed Scopus Google rhamnosus GG weeks6 months6 et al. R. G. et of selected probiotic on the development of PubMed Scopus Google Bifidobacterium lactis lactis weeks12 et al. R, T. Probiotics in pregnant women to allergic disease: a randomized, double-blind trial. J rhamnosus Bifidobacterium Lactobacillus weeks3 et al. Ahn et al. of probiotic Bifidobacterium Lactobacillus in the primary prevention of eczema: A double-blind, randomized, placebo-controlled trial. Allergy Immunol. Bifidobacterium lactis Lactobacillus weeks3 et al. S, et al. Lactobacillus GG during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy. rhamnosus GG 53103)4 et al. et and probiotics reduces maternal but not allergic diseases: A randomized, double-blind, placebo-controlled Exp Allergy. PubMed Scopus Google rhamnosus GG 53103)4 months6 months6 et al. S. M. et al.Probiotics and atopic A double-blind randomised controlled Google most of Lactobacillus lactis Bifidobacterium weeks6 months6 monthsRautava et al. S. E. Salminen S. Isolauri E. probiotic supplementation during pregnancy and reduces the risk of in the infant.J Allergy Clin Immunol. Full Text Full Text PDF PubMed Scopus Google rhamnosus Bifidobacterium (ATCC Bifidobacterium (ATCC of a subgroup of patients previous analyzed by Kalliomaki et al. [4.Kalliomaki 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;357:1076–9.Google of a subgroup of patients previous analyzed by Kukkonen et al. [7.Kukkonen K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar] in a Table clinical related to the of in 15 trials included in the meta-analysis for the guideline’s Question 1: “Should probiotics vs. no probiotics be used in pregnant of for at the of of et al. 2001 [4.Kalliomaki 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;357:1076–9.Google et al. 2002 [5.Rautava S. Kalliomaki M. Isolauri E. Probiotics during pregnancy and breastfeeding might confer immunomodulatory protection against atopic disease in the infant.J Allergy Clin Immunol. 2002; 109: 119-121Abstract Full Text Full Text PDF PubMed Scopus (484) Google Scholar]aAnalysis of a subgroup of patients previous analyzed by Kalliomaki et al. 15 et al. 2007 [6.Abrahamsson TR, Jakobsson T, Bottcher MF, Fredrikson M, Jenmalm MC, Bjorksten B, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119:1174–80.Google et al. 2007 [7.Kukkonen K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google et al. 2008 [8.Huurre A, Laitinen K, Rautava S, Korkeamäki M, Isolauri E. Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: A double-blind placebo-controlled study. Clin Exp Allergy. 2008;38:1342–8.Google with maternal et al. 2008 [9.Marschan E. Kuitunen M. Kukkonen K. Poussa T. Sarnesto A. Haahtela T. et al.Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.Clin Exp Allergy. 2008; 38: 611-618Crossref PubMed Scopus (144) Google Scholar]bAnalysis of a subgroup of patients previous analyzed by Kukkonen et al. of et al. 2008 [10.Wickens K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google et al. 2008 A. R. placebo-controlled of probiotics for primary no clinical of Lactobacillus GG 2008; PubMed Scopus Google to et al. R. G. et of selected probiotic on the development of PubMed Scopus Google et al. R, T. Probiotics in pregnant women to allergic disease: a randomized, double-blind trial. J et al. Ahn et al. of probiotic Bifidobacterium Lactobacillus in the primary prevention of eczema: A double-blind, randomized, placebo-controlled trial. Allergy Immunol. et al. S, et al. Lactobacillus GG during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy. et al. et and probiotics reduces maternal but not allergic diseases: A randomized, double-blind, placebo-controlled Exp Allergy. PubMed Scopus Google et al. S. M. et al.Probiotics and atopic A double-blind randomised controlled Google et al. S. E. Salminen S. Isolauri E. probiotic supplementation during pregnancy and reduces the risk of in the infant.J Allergy Clin Immunol. Full Text Full Text PDF PubMed Scopus Google and Working E. Allergy Clin Full Text Full Text PDF Scopus Google Lactobacillus Bifidobacterium Lactobacillus of a subgroup of patients previous analyzed by Kalliomaki et al. [4.Kalliomaki 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;357:1076–9.Google of a subgroup of patients previous analyzed by Kukkonen et al. [7.Kukkonen K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar] of in a and Working E. Allergy Clin Full Text Full Text PDF Scopus Google Lactobacillus Bifidobacterium Lactobacillus A about the 15 trials [4.Kalliomaki 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;357:1076–9.Google Scholar, S. Kalliomaki M. Isolauri E. Probiotics during pregnancy and breastfeeding might confer immunomodulatory protection against atopic disease in the infant.J Allergy Clin Immunol. 2002; 109: 119-121Abstract Full Text Full Text PDF PubMed Scopus (484) Google Scholar, TR, Jakobsson T, Bottcher MF, Fredrikson M, Jenmalm MC, Bjorksten B, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119:1174–80.Google Scholar, K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar, A, Laitinen K, Rautava S, Korkeamäki M, Isolauri E. Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: A double-blind placebo-controlled study. Clin Exp Allergy. 2008;38:1342–8.Google Scholar, E. Kuitunen M. Kukkonen K. Poussa T. Sarnesto A. Haahtela T. et al.Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.Clin Exp Allergy. 2008; 38: 611-618Crossref PubMed Scopus (144) Google Scholar, K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, A. R. placebo-controlled of probiotics for primary no clinical of Lactobacillus GG 2008; PubMed Scopus Google Scholar, R. G. et of selected probiotic on the development of PubMed Scopus Google Scholar, R, T. Probiotics in pregnant women to allergic disease: a randomized, double-blind trial. J Scholar, Ahn et al. of probiotic Bifidobacterium Lactobacillus in the primary prevention of eczema: A double-blind, randomized, placebo-controlled trial. Allergy Immunol. Scholar, S, et al. Lactobacillus GG during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy. Scholar, et and probiotics reduces maternal but not allergic diseases: A randomized, double-blind, placebo-controlled Exp Allergy. PubMed Scopus Google Scholar, S. M. et al.Probiotics and atopic A double-blind randomised controlled Google S. E. Salminen S. Isolauri E. probiotic supplementation during pregnancy and reduces the risk of in the infant.J Allergy Clin Immunol. Full Text Full Text PDF PubMed Scopus Google Scholar] is that they are all randomized against they were published 2001 and that is a to be well should be that the of Rautava et al. [5.Rautava S. Kalliomaki M. Isolauri E. Probiotics during pregnancy and breastfeeding might confer immunomodulatory protection against atopic disease in the infant.J Allergy Clin Immunol. 2002; 109: 119-121Abstract Full Text Full Text PDF PubMed Scopus (484) Google Scholar] a of patients previous by Kalliomaki et al. [4.Kalliomaki 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;357:1076–9.Google Scholar], as well as et al. [9.Marschan E. Kuitunen M. Kukkonen K. Poussa T. Sarnesto A. Haahtela T. et al.Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.Clin Exp Allergy. 2008; 38: 611-618Crossref PubMed Scopus (144) Google Scholar] analyzed a subgroup of patients by Kukkonen et al. [7.Kukkonen K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar]. all studies patients with of atopy as for that at risk of atopy should be the of a preventive intervention with probiotic The of included in the trials is but the of probiotic or of probiotics used is different the the Authors we have to a of the and in of it was not to analyze the in each the of individual probiotic This is clearly in the but it deserves some particular The probiotic associated with to the World Organization definition of a Working on Guidelines for the Evaluation of Probiotics in Scholar], the probiotics to in confer a health benefit on the Probiotics may by different as well as the Authors have that it is important to also if the is the same or if there are of the different probiotics used in the different Since a literature is available on we can for the related to Lactobacillus the most used probiotic A recent examined of Lactobacillus rhamnosus from different food and from the A, R, M, et al. and of Lactobacillus rhamnosus and with Scholar] by a and A of with different have been by the Authors to the two most common and The A seems to be related to a to to such as but also to the of some in the in the and to to different The a to to different and resources with different and different on the A recent analyzed the and Lactobacillus a likely of two Lactobacillus rhamnosus and were in the the of with the probiotic Lactobacillus rhamnosus GG (ATCC does not in the of of Lactobacillus rhamnosus clinical from of of a 2014; PubMed Scopus Google Scholar]. a Lactobacillus from of Lactobacillus rhamnosus GG Lactobacillus rhamnosus Lactobacillus rhamnosus Lactobacillus Lactobacillus and Lactobacillus different as well as different in and in the to to R. J. A. of Lactobacillus from and and to a common PubMed Scopus Google Scholar]. the Authors also point we that this evidence is a critical point for the definition of the quality of the as In the selected different have been used in it is necessary to different of and in the in to the different of different of The Lactobacillus rhamnosus GG (ATCC 55103) is the most and in but the from studies that use this of probiotic would be The of in the pregnancy is all and it from 2 to the of the 15 selected we considered the clinical features associated with the of to analyze the question 1 of the guideline and we reported in Table The of was a to the of atopic in most it of The used for the of atopic are the most in the and G. features of atopic Scholar] and the The Working for atopic J PubMed Scopus Google Scholar]. The of patients with a the of the patients, the quality of the available seems to be for the is more to the results on the of with its two clinical the IgE-associated and in the clinical features and in the other allergic diseases. IgE-associated are more to the in allergic and if there is also a to The in Table 2 at the of the two trials [5.Rautava S. Kalliomaki M. Isolauri E. Probiotics during pregnancy and breastfeeding might confer immunomodulatory protection against atopic disease in the infant.J Allergy Clin Immunol. 2002; 109: 119-121Abstract Full Text Full Text PDF PubMed Scopus (484) Google Scholar, E. Kuitunen M. Kukkonen K. Poussa T. Sarnesto A. Haahtela T. et al.Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.Clin Exp Allergy. 2008; 38: 611-618Crossref PubMed Scopus (144) Google Scholar] that analyzed of patients of studies [4.Kalliomaki 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;357:1076–9.Google Scholar, K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar]. studies [4.Kalliomaki 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;357:1076–9.Google Scholar, K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar, K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, R, T. Probiotics in pregnant women to allergic disease: a randomized, double-blind trial. J Scholar, Ahn et al. of probiotic Bifidobacterium Lactobacillus in the primary prevention of eczema: A double-blind, randomized, placebo-controlled trial. Allergy Immunol. Scholar, S. E. Salminen S. Isolauri E. probiotic supplementation during pregnancy and reduces the risk of in the infant.J Allergy Clin Immunol. Full Text Full Text PDF PubMed Scopus Google Scholar] a in the of of in the with probiotics if with the other studies [6.Abrahamsson TR, Jakobsson T, Bottcher MF, Fredrikson M, Jenmalm MC, Bjorksten B, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119:1174–80.Google Scholar, A, Laitinen K, Rautava S, Korkeamäki M, Isolauri E. Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: A double-blind placebo-controlled study. Clin Exp Allergy. 2008;38:1342–8.Google Scholar, K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, A. R. placebo-controlled of probiotics for primary no clinical of Lactobacillus GG 2008; PubMed Scopus Google R. G. et of selected probiotic on the development of PubMed Scopus Google Scholar, S, et al. Lactobacillus GG during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy. Scholar, et and probiotics reduces maternal but not allergic diseases: A randomized, double-blind, placebo-controlled Exp Allergy. PubMed Scopus Google S. M. et al.Probiotics and atopic A double-blind randomised controlled Google Scholar] the two The of et al. [10.Wickens K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar] is considered as the Lactobacillus rhamnosus was that with Bifidobacterium lactis was not In of these the can be to the of IgE-associated eczema: studies a [6.Abrahamsson TR, Jakobsson T, Bottcher MF, Fredrikson M, Jenmalm MC, Bjorksten B, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119:1174–80.Google Scholar, K. Savilahti E. Haahtela T. Juntunen-Backman K. Korpela R. Poussa T. et al.Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: A randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2007; 119: 192-198Abstract Full Text Full Text PDF PubMed Scopus (587) Google Scholar, K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, S. M. et al.Probiotics and atopic A double-blind randomised controlled Google Scholar], studies [10.Wickens K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar, R. G. et of selected probiotic on the development of PubMed Scopus Google Scholar, R, T. Probiotics in pregnant women to allergic disease: a randomized, double-blind trial. J Ahn et al. of probiotic Bifidobacterium Lactobacillus in the primary prevention of eczema: A double-blind, randomized, placebo-controlled trial. Allergy Immunol. Scholar] of et al. [10.Wickens K. Black P.N. Stanley T.V. Mitchell E. Fitzharris P. Tannock et effect of 2 probiotics in the prevention of and A double-blind, randomized, placebo-controlled trial.J Allergy Clin Immunol. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar] was considered the of the of allergic by results in two in it was not important in this guideline is the of The consideration also an review of a by the S. R. et al.Probiotics for the prevention and of A systematic review and PubMed Scopus Google Scholar], not and in it not an some in the study. the reported in these 15 trials are and clinical the probiotics and This guideline indicates the of evidence of efficacy of probiotic supplementation in the primary prevention of In the recommendation the guideline panel probiotics in pregnant women at risk for allergy in because considering all critical outcomes, there is a net benefit resulting primarily from prevention of quality in the of this recommendation is also the other two clinical