New insights into the hygiene hypothesis in allergic diseases: mediation of sibling and birth mode effects by the gut microbiota.

There is convincing evidence from both human and animal studies suggesting that the infant intestinal microbiota plays an important role in regulating immune responses associated with the development of allergic diseases. To date there are, however, still no definite bacterial taxa or particular subsets of the microbiota that have been consistently associated with allergic diseases, which is mainly attributable to the methodological dissimilarities between studies. As such there is a need to apply different methodological concepts to enhance a deeper and more refined understanding of the relationship between the gut microbiota and allergies. Within our recent studies we reported that colonization by clostridia in early infancy increased the risk of atopic dermatitis. Using subsequent mediation analysis, we demonstrated that birth mode and having older siblings strongly impacted the infant microbiota which in turn affected the risk of atopic dermatitis. The results of these mediation analyses contributed stronger evidence for a causal link of birth mode and birth order on allergy risk through modulation of the microbiota composition.