In the 1990s it was noted that the composition of the intestinal microbiota or gut flora is different in infants who develop eczema from those without eczema, and that these differences are present before the onset of clinical disease [1, 2]. This finding led to the hypothesis that modification of the intestinal flora in early life might be an effective method for treating or preventing eczema. Two approaches to doing this that have been tested are probiotic supplements and prebiotic supplements. Probiotics are live, non-pathogenic organisms with a beneficial health effect, commonly Lactobacillus or Bifidobacterium strains. Prebiotics are non-digestible oligosaccharides which promote the growth of certain bacterial species, such as Bifidobacteria, in the intestine.
A number of randomised controlled trials in this area have now been undertaken, and in the last year three relevant systematic reviews have been published [3-5]. A Cochrane Review by Osborn and Sinn assessed the effectiveness of prebiotics for the prevention of eczema, among other allergic diseases [3], and identified two randomised controlled trials of prebiotic supplementation in the first months of life. The pooled data from these two trials suggested no overall effect. However, the trials differed significantly in study population, intervention and outcome. In one trial, prebiotic treatment failed to reduce the risk of eczema, while in the other, prebiotic treatment was found to be effective for eczema prevention. The positive trial addressed a very specific population—infants with a family history of allergic disease who had formula feeding introduced within the first two weeks of life, who were formula-fed using an extensively hydrolysed whey formula, and who completely stopped breast feeding before 6 weeks of age [6]. Further prebiotic eczema prevention trials are underway internationally, which will clarify the effects of prebiotic supplementation in different populations. If prebiotics do have a role in eczema prevention, their role is likely to be as an additive to infant formula, where exclusive breast feeding cannot be maintained during the first weeks of life.
A second Cochrane Review by the same team of Osborn and Sinn included an evaluation of the effectiveness of probiotics for the prevention of allergic diseases, including eczema [4]. This review identified six randomised controlled trials of probiotic supplementation in early life where eczema was evaluated as an outcome. The authors found that overall probiotic supplementation reduces the risk of eczema by 18% (RR 0.82, 95% CI 0.70-0.95). There are two caveats to this exciting finding. Firstly, the authors included data from the same randomised controlled trial twice, from two different journal articles [7, 8], which resulted in an exaggeration of the effect of probiotic treatment. If the data of Rautava et al. (which were also included in the publication of Kalliomaki et al.) are excluded from meta-analysis, then the beneficial effect of probiotics becomes statistically non-significant (RR 0.86, 95% CI 0.66-1.12). Secondly, there is significant heterogeneity between the individual studies—in the probiotic strain used, the treatment regimen and the study outcome. For example, some studies used probiotics to treat women during pregnancy, some treated mothers during breast feeding, and some gave them directly to infants postnatally. In view of these caveats, the role of probiotics for preventing eczema remains a subject for further investigation, rather than clinical practice at present.
The final systematic review, by Lee and colleagues, evaluated the efficacy of probiotics for preventing and also treating eczema [5]. These authors calculated a significant, 31% reduction in risk of eczema when probiotics are used for eczema prevention, but no significant benefit from using probiotics to treat established eczema. This review has significant methodological limitations, including a suboptimal search strategy and problems with the meta-analyses. In particular, the apparent preventive effect of probiotics was magnified by the inclusion of data from the same patients more than three times, deriving from duplicate publications. The authors have, however, highlighted the lack of evidence that probiotics are an effective treatment for established eczema, in contrast to the promising data that probiotics may have a role in eczema prevention.
The use of prebiotics or probiotics for preventing eczema is an exciting area of study. These systematic reviews suggest that such treatments are not yet at a stage where they can be recommended for use in clinical practice, but there are grounds for optimism that they will play a role in future strategies for eczema prevention.
References
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Link to PubMed Abstract
2. 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;107:129-34.
Link to PubMed Abstract
3. Osborn DA, Sinn JK. Prebiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev. 2007(4):CD006474.
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4. Osborn DA, Sinn JK. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev. 2007(4):CD006475.
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5. 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. e11.
Link to PubMed Abstract
6. Moro G, Arslanoglu S, Stahl B, Jelinek J, Wahn U, Boehm G. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child. 2006;91:814-9.
Link to PubMed Abstract
7. 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;357:1076-9.
Link to PubMed Abstract
8. Rautava S, Kalliomäki M, Isolauri E. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. J Allergy Clin Immunol. 2002;109:119-21.
Link to PubMed Abstract
