Influence of pro- and prebiotics on sensitization and allergic diseases and the association between cord-specific IgG and early- versus late-onset eczema and allergy prevalence in adolescence

Allergic diseases are common; worldwide over 7% of children at 6–7 or 13–14 years of age have eczema and 14% of adolescents at 13–14 years have respiratory allergic disease, i.e., asthma and/or allergic rhinitis (AR) (1). Prevalence of allergic diseases has increased in developed countries during last decades (2). At last years the prevalence of allergic symptoms has increased also in developing countries (3). The aetiology of allergic diseases is complex, involving both host genetic and environmental life-style factors and interactions between them (4). The financial burden of allergies is high. In Finland, with five million inhabitants, the cost of allergic diseases was about 1.3–1.6 billion euros in 2011 (5). WHO characterized probiotics as “live micro-organisms which, when administered in adequate dosage, confer a health benefit on the host”(6). The use of probiotics is safe in healthy persons (7). The effects of probiotics are species- and strain-dependent (8). Prebiotics are characterized as ‘‘a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health’’ (9). Microbiota of the colon can ferment the prebiotics to short-chain fatty acids which can have an effect on immune system (10). We carried out a randomized double-blind placebo-controlled study in children at high-risk of allergy to define whether the use of pre- and postnatal pre- and probiotics decreases the prevalence of allergic diseases for up to 10 years (study I) or the prevalence of immunoglobulin E (IgE) sensitization for up to 13 years (study II). We also investigated the association between the presence of cord blood (cB) allergen-specific immunoglobulin G (IgG) and IgE (study IV)and the time of early- (under one year of age diagnosed) and late-onset (≥1 year of age diagnosed) eczema (study III) with allergic diseases in children up to 13 years of age. Mothers carrying a foetus with at least one atopic parent in Helsinki area in 2000-2003 were recruited for the study. In probiotic group 610 and in placebo group 613 mothers with high-risk infant were assigned in. At two years of age 461 and 463, at five years 445 and 446, at 10 years 400 and 407 and at 13 years 330 and 312 in the probiotic group in the placebo group completed the follow-up. Mothers in the probiotic group received probiotic capsules from gestational week 35 and their children received open probiotic capsules mixed with syrup of prebiotics for six months after birth. Mothers and children in the placebo group received the same kind of capsules without probiotics or syrup of prebiotics. No significant difference was found up to 10 years in the lifetime prevalence of any allergic disease between the two groups. However, in the probiotic group the lifetime prevalence of eczema was lower up to 10 years compared with that in the placebo group. Further, in the probiotic group the prevalence of allergic rhino-conjunctivitis was higher than in the placebo group at 5–10 years. No significant difference was discovered in the prevalence rates of allergic sensitization between the probiotic and placebo groups at two and five years. However, in the probiotic group the prevalence of IgE sensitization to cat/dog dander was higher than in the placebo group at 13 years, with no significant difference at two or five years. IgE sensitization to seasonal pollens was higher in the probiotic group than in the placebo group at two years in the subgroup of vaginally delivered children, but no significant difference was detected at five or 13 years in that subgroup or the total cohort. Early-onset eczema was associated with asthma and IgE-associated asthma as well as with IgE-associated allergic rhinitis up to 13 years of age. Late-onset eczema showed an association only with IgE-associated allergic rhinitis up to 13 years. Elevated levels of cB-IgG antibodies against birch were associated with more allergic diseases, rhinitis, IgE-associated allergic diseases and IgE-associated rhinitis up to 13 years, as well as with more IgE-associated eczema up to five years. Elevated levels of cB-IgE against birch were associated with less eczema, whereas higher levels of cB-IgE against milk were associated with more rhinitis up to 13 years of age. In conclusion, our findings indicate that pre- and postnatal use of a mixture of pro- and prebiotics can still affect the prevalence of allergic diseases and sensitization at adolescence. In high-risk children, use of a mixture of pro- and prebiotics was associated with a lower lifetime prevalence of eczema, but also with more allergic rhinitis at 5–10 years. Even though we found no significant difference in the prevalence of IgE sensitization to the tested allergens between the probiotic and placebo groups at two and five years, surprisingly, children given probiotics were more often IgE-sensitized to animal dander at 13 years than children given placebo. It is difficult to predict at birth or childhood who is going to have allergic disease later in life, even though higher levels of cB-IgG antibodies against birch were associated with more allergic diseases, and early-onset eczema was associated with all respiratory allergic diseases at adolescence. It is important to treat atopic eczema well in infants.