The Effectiveness of Probiotics in Treating Food and Cow’s Milk Allergies among Pediatric Age Group: A Meta-analysis of Randomized Controlled Trials
Abstract
The global prevalence of allergies is on the rise. Food allergies are of special concern among children under 5 years of age, leading to morbidity and mortality. Though the standard management is avoidance, probiotics are being used widely to prevent and treat food allergies.
We aimed to determine the effect of probiotics as a therapeutic option for controlling food and cow’s milk allergy among children under 5 years of age. A systematic search of electronic medical literature databases was conducted. We included all eligible randomized controlled trials available from inception until May 2021. The primary outcome of interest was the relief of allergic symptoms, while the secondary outcome was the induction of tolerance. Two investigators undertook the literature search, screening, data extraction, and quality appraisal independently. Data analysis and synthesis were performed using STATA 14 software. Subgroup analysis was performed for the duration of use and follow-up, and the age category of children included in the outcome were done.
Twenty trials involving 4043 pediatric patients with food allergies were included in the review. Subgroup analysis also revealed that probiotics were effective in treating food allergies across the various subgroups included in the model. Around 15 trials reported our primary outcome, relief of symptoms, as a binary variable, which was pooled to obtain a risk ratio of 0.86 (95% confidence interval [CI], 0.77–0.95), with very low heterogeneity (I2 7.7%). Six trials were included for the secondary outcome of interest, which gave an imprecise pooled estimate of 1.29 (95% CI, 0.98–1.70) with significant heterogeneity (I2 7).
Thus, we conclude that probiotics can serve as a vital therapeutic option in tackling food allergies among children less than 5 years of age. Further larger studies exploring the effectiveness of individual strains and their safety pattern are essential.
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3. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and Management of Food Allergy in the United States: summary of the NIAID-sponsored expert panel report. Nutr Res. 2011;31(1):61–75.
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7. Vandenplas Y, Huys G, Daube G. Probiotics: an update. J Pediatr. 2015;91(1):6–21.
8. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement.2009. PLoS Med. 6(7):e1000097.
9. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;18;343.
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11. 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(1):192-8.
12. Rautava S, Arvilommi H, Isolauri E. Specific probiotics in enhancing maturation of IgA responses in formula-fed infants. Pediatr Res. 2006;60(2):221-4.
13. Wickens K, Black PN, Stanley TV, Mitchell E, Fitzharris P, Tannock GW, et al. Probiotic Study Group. A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2008;122(4):788-94.
14. Kim JY, Kwon JH, Ahn SH, Lee SI, Han YS, Choi YO, et al. Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double‐blind, randomized, placebo‐controlled trial. Pediatr Allergy Immunol. 2010;21(2p2):e386-93.
15. Kuitunen M, Kukkonen AK, Savilahti E. Impact of maternal allergy and use of probiotics during pregnancy on breast milk cytokines and food antibodies and development of allergy in children until 5 years. Int Archives Allergy Immunol. 2012;159(2):162-70.
16. Niers L, Martín R, Rijkers G, Sengers F, Timmerman H, Van Uden N et al. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy. 2009;64(9):1349-58.
17. Soh SE, Aw M, Gerez I, Chong YS, Rauff M, Ng YP, 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. Clin Experimental Allergy. 2009;39(4):571-8.
18. Baldassarre ME, Laforgia N, Fanelli M, Laneve A, Grosso R, Lifschitz C. Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone. J Pediatr. 2010;156(3):397-401.
19. Wu FL, Feng XB, Liu XX, LI YY. The influence of Bifidobateria on the composition of breast milk and the relationship between Bifidobacteria and the incidence of allergic diseases in breast-fed infants. J Clin Pediatr. 2010;28:260-3.
20. Canani RB, Di Costanzo M, Bedogni G, Amoroso A, Cosenza L, Di Scala C, et al. Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial. J Allergy Clin Immunol. 2017;139(6):1906-13.
21. Basturk A, Isik İ, Atalay A, Yılmaz A. Investigation of the efficacy of Lactobacillus rhamnosus GG in infants with cow’s milk protein allergy: a randomised double-blind placebo-controlled trial. Probiotics Antimicrob proteins. 2020;12(1):138-43.
22. Plummer EL, Chebar L, Tobin JM, Uebergang JB, Axelrad C, Garland SM, et al. ProPrems Study Group. Postnatal probiotics and allergic disease in very preterm infants: Sub‐study to the ProPrems randomized trial. Allergy. 2020;75(1):127-36.
23. Nocerino R, Di Costanzo M, Bedogni G, Cosenza L, Maddalena Y, Di Scala C, et al. Dietary treatment with extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG prevents the occurrence of functional gastrointestinal disorders in children with cow's milk allergy. J Pediatr. 2019;213(21):137-42.
24. Cukrowska B, Ceregra A, Maciorkowska E, Surowska B, Zegadło-Mylik MA, Konopka E, et al. The Effectiveness of Probiotic Lactobacillus rhamnosus and Lactobacillus casei Strains in Children with Atopic Dermatitis and Cow’s Milk Protein Allergy: A Multicenter, Randomized, Double Blind, Placebo Controlled Study. Nutrients. 2021;13(4):1169.
25. Canani RB, Di Costanzo M. Gut microbiota as potential therapeutic target for the treatment of cow’s milk allergy. Nutrients. 2013;5(3):651-62.
26. Hol J, van Leer EH, Schuurman BE, de Ruiter LF, Samsom JN, Hop W, et al. The acquisition of tolerance toward cow's milk through probiotic supplementation: a randomized, controlled trial. J Allergy Clin Immunol. 2008;121(6):1448-54.
27. Berni Canani R, Nocerino R, Terrin G, Frediani T, Lucarelli S, Cosenza L, et al. Formula selection for management of children with cow’smilk allergy influences the rate of acquisition of tolerance: a prospectivemulticenter study. J Pediatr. 2013;163(3):771– 777.e1.
28. Canani RB, Bedogni G, Cosenza L, Amoroso A, Di Costanzo M, Di Scala C, et al. Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG prevents the occurrence of other allergic manifestations in subjects with cow's milk allergy: 3-year randomized controlled trial. Dig Liver Dis. 2016;48:e279.
29. Cukrowska B, Ceregra A, Klewicka E, Śliżewska K, Motyl I, Libudzisz Z. Probiotyczne Szczepy Lactobacillus Casei I Lactobacillus Paracasei W Leczeniu Alergii Pokarmowej U Dzieci. Przeglad Pediatryczny. 2010 1;40(1).
30. Savilahti E. Probiotics in the treatment and prevention of allergies in children: review. Bioscience Microflora. 2011;30(4):119–28.
31. Miraglia del Giudice M, De Luca MG. The role of probiotics in the clinical management of food allergy and atopic dermatitis. J Clin Gastroenterol. 2004;38(6 Suppl):S84–5
32. Miro-Blanch J, Yanes O. Epigenetic regulation at the interplay between gut microbiota and host metabolism. Front Genet. 2019;10(6):638.
33. Kuitunen M. Probiotics and prebiotics in preventing food allergy and eczema. Curr Opin Allergy Clin Immunol. 2013;13(8):280–6.
34. West CE, Jenmalm MC, Prescott SL. The gut microbiota and its role in the development of allergic disease: a wider perspective. Clin Exp Allergy. 2015;45(2):43–53.
35. Tan-Lim CS, Esteban-Ipac NA. Probiotics as treatment for food allergies among pediatric patients: a meta-analysis. World Allergy Organ J. 2018;11(1):1-3.
36. Zhang GQ, Hu HJ, Liu CY, Zhang Q, Shakya S, Li ZY. 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).
37. Qamer S, Deshmukh M, Patole S. Probiotics for cow’s milk protein allergy: a systematic review of randomized controlled trials. European J Pediatr. 2019;178(8):1139-49.
2. Savage J, Johns CB. Food allergy: epidemiology and natural history. Immunol Allergy Clin N Am. 2015;35(1):45–59.
3. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and Management of Food Allergy in the United States: summary of the NIAID-sponsored expert panel report. Nutr Res. 2011;31(1):61–75.
4. Rokaite R, Labanauskas L. Gastrointestinal disorders in children with atopic dermatitis. Medicina (Kaunas). 2005;41(10):837-45. English, Lithuanian. PMID: 16272830.
5. Lee AJ, Thalayasingam M, Lee BW. Food allergy in Asia: how does it compare? Asia Pac Allergy. 2013;3(1):3–14.
6. Food and Agriculture Organization, World Health Organization. Guidelines for the evaluation of probiotics in food. In: Report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in food. 2002. http://www.who.int/foodsafety/fs_management/en/probiotic_ guidelines.pdf. Accessed 24 August 2021.
7. Vandenplas Y, Huys G, Daube G. Probiotics: an update. J Pediatr. 2015;91(1):6–21.
8. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement.2009. PLoS Med. 6(7):e1000097.
9. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;18;343.
10. Abrahamsson TR, Jakobsson T, Böttcher MF, Fredrikson M, Jenmalm MC, Björkstén B, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007;119(5):1174-80.
11. 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(1):192-8.
12. Rautava S, Arvilommi H, Isolauri E. Specific probiotics in enhancing maturation of IgA responses in formula-fed infants. Pediatr Res. 2006;60(2):221-4.
13. Wickens K, Black PN, Stanley TV, Mitchell E, Fitzharris P, Tannock GW, et al. Probiotic Study Group. A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2008;122(4):788-94.
14. Kim JY, Kwon JH, Ahn SH, Lee SI, Han YS, Choi YO, et al. Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double‐blind, randomized, placebo‐controlled trial. Pediatr Allergy Immunol. 2010;21(2p2):e386-93.
15. Kuitunen M, Kukkonen AK, Savilahti E. Impact of maternal allergy and use of probiotics during pregnancy on breast milk cytokines and food antibodies and development of allergy in children until 5 years. Int Archives Allergy Immunol. 2012;159(2):162-70.
16. Niers L, Martín R, Rijkers G, Sengers F, Timmerman H, Van Uden N et al. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy. 2009;64(9):1349-58.
17. Soh SE, Aw M, Gerez I, Chong YS, Rauff M, Ng YP, 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. Clin Experimental Allergy. 2009;39(4):571-8.
18. Baldassarre ME, Laforgia N, Fanelli M, Laneve A, Grosso R, Lifschitz C. Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone. J Pediatr. 2010;156(3):397-401.
19. Wu FL, Feng XB, Liu XX, LI YY. The influence of Bifidobateria on the composition of breast milk and the relationship between Bifidobacteria and the incidence of allergic diseases in breast-fed infants. J Clin Pediatr. 2010;28:260-3.
20. Canani RB, Di Costanzo M, Bedogni G, Amoroso A, Cosenza L, Di Scala C, et al. Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial. J Allergy Clin Immunol. 2017;139(6):1906-13.
21. Basturk A, Isik İ, Atalay A, Yılmaz A. Investigation of the efficacy of Lactobacillus rhamnosus GG in infants with cow’s milk protein allergy: a randomised double-blind placebo-controlled trial. Probiotics Antimicrob proteins. 2020;12(1):138-43.
22. Plummer EL, Chebar L, Tobin JM, Uebergang JB, Axelrad C, Garland SM, et al. ProPrems Study Group. Postnatal probiotics and allergic disease in very preterm infants: Sub‐study to the ProPrems randomized trial. Allergy. 2020;75(1):127-36.
23. Nocerino R, Di Costanzo M, Bedogni G, Cosenza L, Maddalena Y, Di Scala C, et al. Dietary treatment with extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG prevents the occurrence of functional gastrointestinal disorders in children with cow's milk allergy. J Pediatr. 2019;213(21):137-42.
24. Cukrowska B, Ceregra A, Maciorkowska E, Surowska B, Zegadło-Mylik MA, Konopka E, et al. The Effectiveness of Probiotic Lactobacillus rhamnosus and Lactobacillus casei Strains in Children with Atopic Dermatitis and Cow’s Milk Protein Allergy: A Multicenter, Randomized, Double Blind, Placebo Controlled Study. Nutrients. 2021;13(4):1169.
25. Canani RB, Di Costanzo M. Gut microbiota as potential therapeutic target for the treatment of cow’s milk allergy. Nutrients. 2013;5(3):651-62.
26. Hol J, van Leer EH, Schuurman BE, de Ruiter LF, Samsom JN, Hop W, et al. The acquisition of tolerance toward cow's milk through probiotic supplementation: a randomized, controlled trial. J Allergy Clin Immunol. 2008;121(6):1448-54.
27. Berni Canani R, Nocerino R, Terrin G, Frediani T, Lucarelli S, Cosenza L, et al. Formula selection for management of children with cow’smilk allergy influences the rate of acquisition of tolerance: a prospectivemulticenter study. J Pediatr. 2013;163(3):771– 777.e1.
28. Canani RB, Bedogni G, Cosenza L, Amoroso A, Di Costanzo M, Di Scala C, et al. Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG prevents the occurrence of other allergic manifestations in subjects with cow's milk allergy: 3-year randomized controlled trial. Dig Liver Dis. 2016;48:e279.
29. Cukrowska B, Ceregra A, Klewicka E, Śliżewska K, Motyl I, Libudzisz Z. Probiotyczne Szczepy Lactobacillus Casei I Lactobacillus Paracasei W Leczeniu Alergii Pokarmowej U Dzieci. Przeglad Pediatryczny. 2010 1;40(1).
30. Savilahti E. Probiotics in the treatment and prevention of allergies in children: review. Bioscience Microflora. 2011;30(4):119–28.
31. Miraglia del Giudice M, De Luca MG. The role of probiotics in the clinical management of food allergy and atopic dermatitis. J Clin Gastroenterol. 2004;38(6 Suppl):S84–5
32. Miro-Blanch J, Yanes O. Epigenetic regulation at the interplay between gut microbiota and host metabolism. Front Genet. 2019;10(6):638.
33. Kuitunen M. Probiotics and prebiotics in preventing food allergy and eczema. Curr Opin Allergy Clin Immunol. 2013;13(8):280–6.
34. West CE, Jenmalm MC, Prescott SL. The gut microbiota and its role in the development of allergic disease: a wider perspective. Clin Exp Allergy. 2015;45(2):43–53.
35. Tan-Lim CS, Esteban-Ipac NA. Probiotics as treatment for food allergies among pediatric patients: a meta-analysis. World Allergy Organ J. 2018;11(1):1-3.
36. Zhang GQ, Hu HJ, Liu CY, Zhang Q, Shakya S, Li ZY. 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).
37. Qamer S, Deshmukh M, Patole S. Probiotics for cow’s milk protein allergy: a systematic review of randomized controlled trials. European J Pediatr. 2019;178(8):1139-49.
| Files | ||
| Issue | Vol 22 No 2 (2023) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i2.12674 | |
| Keywords | ||
| Food allergy Meta-analysis Milk hypersensitivity Probiotics Randomized control trials | ||
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How to Cite
1.
Feng H, Wu Y. The Effectiveness of Probiotics in Treating Food and Cow’s Milk Allergies among Pediatric Age Group: A Meta-analysis of Randomized Controlled Trials. Iran J Allergy Asthma Immunol. 2023;22(2):124-137.
