Probiotics in the prevention of eczema: a randomised controlled trial

Stephen J Allen, Sue Jordan, Melanie Storey, Catherine A Thornton, Michael B Gravenor, Iveta Garaiova, Susan F Plummer, Duolao Wang, Gareth Morgan, Stephen J Allen, Sue Jordan, Melanie Storey, Catherine A Thornton, Michael B Gravenor, Iveta Garaiova, Susan F Plummer, Duolao Wang, Gareth Morgan

Abstract

Objective: To evaluate a multistrain, high-dose probiotic in the prevention of eczema.

Design: A randomised, double-blind, placebo-controlled, parallel group trial.

Settings: Antenatal clinics, research clinic, children at home.

Patients: Pregnant women and their infants.

Interventions: Women from 36 weeks gestation and their infants to age 6 months received daily either the probiotic (Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20; total of 10(10) organisms/day) or matching placebo.

Main outcome measure: Diagnosed eczema at age 2 years. Infants were followed up by questionnaire. Clinical examination and skin prick tests to common allergens were done at 6 months and 2 years.

Results: The cumulative frequency of diagnosed eczema at 2 years was similar in the probiotic (73/214, 34.1%) and placebo arms (72/222, 32.4%; OR 1.07, 95% CI 0.72 to 1.6). Among the secondary outcomes, the cumulative frequency of skin prick sensitivity at 2 years was reduced in the probiotic (18/171; 10.5%) compared with the placebo arm (32/173; 18.5%; OR 0.52, 95% CI 0.28 to 0.98). The statistically significant differences between the arms were mainly in sensitisation to cow's milk and hen's egg proteins at 6 months. Atopic eczema occurred in 9/171 (5.3%) children in the probiotic arm and 21/173 (12.1%) in the placebo arm (OR 0.40, 95% CI 0.18 to 0.91).

Conclusions: The study did not provide evidence that the probiotic either prevented eczema during the study or reduced its severity. However, the probiotic seemed to prevent atopic sensitisation to common food allergens and so reduce the incidence of atopic eczema in early childhood.

Trial registration number: ISRCTN26287422.

Keywords: Allergy; Dermatology; Microbiology.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Trial profile *Reasons for exclusion: pregnancy complication (n=110); presented after 36 weeks gestation or at the end of the recruitment period and before 36 weeks gestation (83); multiple pregnancy (14); contacted again after recruitment terminated (9); previous infant participated in trial (6); unwilling to stop current probiotic (1). †Reasons for failure to participate: lost contact with research team (288); not sufficiently interested or disliked tests (184); concern that trial was “too much to take on” (129); unwillingness to take the investigation products (85); not prepared to be allocated to the placebo arm (21); developed a medical condition (16); language difficulties (10); not willing for this child to be treated differently from previous child (7); bereavement (2). ‡Follow-up was often delayed; includes children seen up to, but not including, age 3 years.

References

    1. ISAAC. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee . Lancet 1998;351:1225–32.
    1. Asher MI, Montefort S, Björkstén B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368:733–43.
    1. Odhiambo JA, Williams HC, Clayton TO, et al. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol 2009;124:1251–8.
    1. Flohr C. Recent perspectives on the global epidemiology of childhood eczema. Allergol Immunopathol (Madr) 2011;39:174–82.
    1. Bieber T. Atopic dermatitis. Ann Dermatol 2010;22:125–37.
    1. Arshad SH, Tariq SM, Matthews S, et al. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics 2001;108:E33.
    1. Wüthrich B, Schmid-Grendelmeier P. The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated ("extrinsic") and the nonallergic (“intrinsic”) AEDS. J Investig Allergol Clin Immunol 2003;13:1–5.
    1. Illi S, von Mutius E, Lau S, et al. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet 2006;368:763–70.
    1. Strachan DP. Hayfever, hygiene and household size. BMJ 1989;299:1259–60.
    1. Okada H, Kuhn C, Feillet H, et al. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol 2010;160:1–9.
    1. Yoo J, Tcheurekdjian H, Lynch SV, et al. Microbial manipulation of immune function for asthma prevention: inferences from clinical trials. Proc Am Thorac Soc 2007;4:277–82.
    1. FAO/WHO. Report on Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. 2001. (accessed Sep 2013).
    1. Tang ML, Lahtinen SJ, Boyle RJ. Probiotics and prebiotics: clinical effects in allergic disease. Curr Opin Pediatr 2010;22:626–34.
    1. Ozdemir O. Various effects of different probiotic strains in allergic disorders: an update from laboratory and clinical data. Clin Exp Immunol 2010;160:295–304.
    1. Allen SJ, Jordan S, Storey M, et al. Dietary supplementation with lactobacilli and bifidobacteria is well tolerated and not associated with adverse events during late pregnancy and early infancy. J Nutr 2010;140:483–8.
    1. Jordan S, Watkins A, Storey M, et al. Volunteer bias in recruitment, retention, and blood sample donation in a randomised controlled trial involving mothers and their children at six months and two years: a longitudinal analysis. PLoS ONE 8: e67912.
    1. Kalliomäki M, Salminen S, Arvilommi H, et al. Probiotics in the primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001;357:1076–9.
    1. Timmerman HM, Koning CJ, Mulder L, et al. Monostrain, multistrain and multispecies probiotics—A comparison of functionality and efficacy. Int J Food Microbiol 2004;96:219–33.
    1. Kunz B, Oranje AP, Labrèze L, et al. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology 1997;195:10–9.
    1. Position paper: allergen standardization and skin tests. The European academy of allergology and clinical immunology. Allergy 1993;48:48–82.
    1. Leung DY, Bieber T. Atopic dermatitis. Lancet 2003;361:151–60.
    1. Kaur B, Anderson HR, Austin J, et al. Prevalence of asthma symptoms, diagnosis, and treatment in 12–14 year old children across Great Britain (international study of asthma and allergies in childhood, ISAAC UK). BMJ 1998;316:118–24.
    1. Wadonda-Kabondo N, Sterne JAC, Golding J, et al. A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0–42 months. Br J Dermatol 2003;149:1023–8.
    1. Pelucchi C, Chatenoud L, Turati F, et al. Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis. Epidemiology 2012;23:402–14.
    1. Wickens K, Black PN, Stanley TV, et al. 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;122:788–94.
    1. Fiocchi A, Burks W, Bahna SL, et al. Clinical use of probiotics in pediatric allergy (CUPPA): a world allergy organization position paper. World Allergy Organ J 2012;5:148–67.
    1. Flohr C. Atopic dermatitis diagnostic criteria and outcome measures for clinical trials: still a mess. J Invest Dermatol 2011;131:557–9.
    1. Elazab N, Mendy A, Gasana J, et al. Probiotic administration in early life, Atopy, and Asthma: a meta-analysis of clinical trials. Pediatrics 2013;132:e666–76.
    1. Kulig M, Bergmann R, Klettke U, et al. Natural course of sensitization to food and inhalant allergens during the first 6 years of life. J Allergy Clin Immunol 1999;103:1173–9.
    1. Abrahamsson TR, Jakobsson T, Bottcher MF, et al. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2007;119:1174–80.
    1. Rose MA, Stieglitz F, Köksal A, et al. Efficacy of probiotic Lactobacillus GG on allergic sensitization and asthma in infants at risk. Clin Exp Allergy 2010;40:1398–405.
    1. Boyle RJ, Ismail IH, Kivivuori S, et al. Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy 2011;66:509–16.
    1. 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. Clin Exp Allergy 2009;39:571–8.
    1. Kopp MV, Hennemuth I, Heinzmann A, et al. Randomized, double-blind, placebo-controlled trial of probiotics for primary prevention: no clinical effects of Lactobacillus GG supplementation. Pediatrics 2008;121:e850–6.
    1. Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life 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 Immunol 2007;119:184–91.
    1. Kalliomaki M, Salminen S, Poussa T, et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003;361:1869–71.
    1. Kukkonen K, Savilahti E, Haahtela 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;119:192–8.
    1. Niers L, Martin R, Rijkers G, et al. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy 2009;64:1349–58.
    1. West CE, Hammarström ML, Hernell O. Probiotics during weaning reduce the incidence of eczema. Pediatr Allergy Immunol 2009;20:430–7.
    1. Kalliomäki M, Antoine JM, Herz U, et al. Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics. J Nutr 2010;140:713S–21S.
    1. Ker J, Hartert TV. The atopic march: what's the evidence? Ann Allergy Asthma Immunol 2009;103:282–9.

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