Probiotics and prebiotics in the primary prevention of allergic diseases

The rapid increase in allergic diseases in developed, high-income countries during recent decades is attributed to several changes in the environment such as urbanization and improved hygiene. This relative lack of microbial stimulation is connected to a delay in maturation of the infantile immune system and seems to predispose especially genetically prone infants to allergic diseases. Probiotics, which are live ingestible health-promoting microbes, may compensate for the lack of microbial stimulation of the developing gut immune system and may thus be beneficial in prevention of allergies. Prebiotics, which are indigestible nutrients by us, promote the growth and activity of a number of bacterial strains considered beneficial for the gut. In a large cohort of 1 223 infants at hereditary risk for allergies we studied in a double-blind placebo-controlled manner whether probiotics administered in early life prevent allergic diseases from developing. We also evaluated their safety and their effects on common childhood infections, vaccine antibody responses, and intestinal immune markers. Pregnant mothers used a mixture of four probiotic bacteria or a placebo, from their 36th week of gestation. Their infants received the same probiotics plus prebiotic galacto-oligosaccharides for 6 months. The 2-year follow-up consisted of clinical examinations and allergy tests, fecal and blood sampling, and regular questionnaires. Among the 925 infants participating in the 2-year follow-up the cumulative incidence of any allergic disease (food allergy, eczema, asthma, rhinitis) was comparable in the probiotic (32%) and the placebo (35%) group. However, eczema, which was the most common manifestation (88%) of all allergic diseases, occurred less frequently in the probiotic (26%) than in the placebo group (32%). The preventive effect was more pronounced against atopic (IgE-associated) eczema which, of all atopic diseases, accounted for 92%. The relative risk reduction of eczema was 26% and of atopic eczema 34%. To prevent one case of eczema, the number of mother-infant pairs needed to treat was 16. Probiotic treatment was safe without any undesirable outcome for neonatal morbidity, feeding-related behavior, serious adverse events, growth, or for vaccine-induced antibody responses. Fewer infants in the probiotic than in the placebo group received antibiotics during their first 6 months of life and thereafter to age 2 years suffered from fewer respiratory tract infections. As a novel finding, we discovered that high fecal immunoglobulin A (IgA) concentrations at age 6 months associated with reduced risk for atopic (IgE-associated) diseases by age 2 years. In conclusion, although feeding probiotics to high-risk newborn infants showed no preventive effect on the cumulative incidence of any allergic diseases by age 2, they apparently prevented eczema. This probiotic effect was more pronounced among IgE-sensitized infants. The treatment was safe and seemed to stimulate maturation of the immune system as indicated by increased resistance to respiratory infections and improved vaccine antibody responses.