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Probiotics and prevention of eczema: have we enough data to draw conclusions?

We read with great interest the article by Zuccotti et al. about the possibility of implementing a primary prevention strategy for allergic diseases (1). This article is conceptually linked to the EAACI Food Allergy and Anaphylaxis Guidelines recommendations (2) that stated ‘there is no evidence to recommend that breastfeeding women should modify their diet or take any supplements such as probiotics in order to prevent food allergy in their children’ and during infancy that ‘there is no evidence to recommend prebiotics or probiotics or other dietary supplements based on particular nutrients to prevent food allergy’. It is also linked to the recently published WAO guidelines (3) which are partially conflicting with the previous conclusion because it suggests that ‘using probiotics in women who breastfeed infants at high risk of developing allergy, because considering all critical outcomes, there is a net benefit resulting primarily from prevention of eczema (conditional recommendation, very low quality evidence)’. We have already commented the above-mentioned discrepancies by supporting the lack of evidence to indicate the use of probiotics in the primary prevention of atopic eczema (4, 5). This systematic review and meta-analysis (1) substantially examine the same patients. The authors describe a significant effect of probiotic supplementation in the reduction of the relative risk for eczema in infants and conclude that ‘the prevention of infantile eczema represents a potential indication for probiotic use during pregnancy and early infancy’ (1). In our opinion, two methodological points determining the bias of the results are questionable. The first point is the inclusion of the same patients at different phases of follow-up in the statistical analysis. In particular, the study conducted by Rautawa et al. (6) was a part of a double-blind, placebo-controlled trial performed by Kalliomaki et al. (7); the study by Prescott et al. (8) represents a follow-up of the same infants recruited and described by Taylor et al. (9). Furthermore, Abrahamsson et al. (10) showed results after a 7-year follow-up of infants from a previous randomized double-blind placebo-controlled trial published in 2007 (11); part of immunological and clinical data of the same infants are also reported in the article by Bottcher et al. (12). Wickens et al. showed in three different articles the outcomes at 2, 4 and 6 years of the same children (13–15). In case of more than one publication or more than one follow-up of the same population, we believe that only data from one study for a specific item (eczema) should be considered and included in a correct statistical analysis. The second point to highlight is the heterogeneity of the probiotics used, as also the WAO guidelines (3) observed. For example, the analysis of a subgroup of patients named ‘sub-meta-analysis’ showed significant effect of probiotic ‘mixtures’ supplementation in the prevention of eczema (RR 0.54 [95% CI: 0.43–0.68], P < 0.00001) (1). Probiotic mixtures used in these studies were all different (Table 1). As the