ORIGINAL ARTICLE EXPERIMENTAL ALLERGY AND IMMUNOLOGY Probiotics in primary prevention of allergic disease – follow-up at 8–9 years of age C. E. West 1 , M.-L. Hammarstr € om 2 & O. Hernell 1 1 Department of Clinical Sciences, Pediatrics, Ume  a University, Ume  a; 2 Department of Clinical Microbiology, Immunology, Ume  a University, Ume  a, Sweden To cite this article: West CE, Hammarstr€ om M-L, Hernell O. Probiotics in primary prevention of allergic disease – follow-up at 8–9 years of age. Allergy 2013; 68: 1015–1020. Keywords allergy prevention; asthma; eczema; Lactobacillus paracasei ssp paracasei F19; nitric oxide. Correspondence Dr. Christina West, Department of Clinical Sciences, Pediatrics, Ume  a University, SE-901 85 Ume  a, Sweden. Tel.: +46 90 7852216 Fax: +46 90 123728 E-mail: christina.west@pediatri.umu.se Accepted for publication 25 April 2013 DOI:10.1111/all.12191 Edited by: Bodo Niggemann Abstract Background: Long-term effects of probiotics in primary prevention of allergic disease need further evaluation. We previously reported a reduced cumulative incidence of infant eczema by feeding Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning. Therefore, we assessed effects of LF19 on the prevalence of allergic disease at school age. Methods: In a double-blind placebo-controlled trial infants were randomized to daily intake of cereals with (n = 89) or without LF19 10 8 CFU (n = 90) from 4–13 months of age. At age 8–9, we evaluated the prevalence of allergic disease (eczema, allergic rhinitis, asthma, and food allergy) by clinical examination and validated questionnaires. IgE sensitization was assessed by skin prick test (inhalant allergens) and specific IgE levels (food allergens). Lung function was evaluated by a spirometry reversibility test. Fractional exhaled nitric oxide (FE NO ) was measured. Results: Of 171 children that completed the intervention, 121 were assessed at age 8–9. In the probiotic group, 15/59 (25%) were diagnosed with any allergic disease vs 22/62 (35%) in the placebo group [OR (95% CI) 0.62 (0.28–1.36)]. Corresponding numbers for IgE-associated allergic disease were 9/53 (17%) vs 12/ 59 (20%) [0.80 (0.31–2.09)]. Median (25th-75th percentile) FE NO was 9 (8–12) in the probiotic vs 8 (7–12) ppb in the placebo group (P > 0.05). There was no effect of LF19 on lung function measures (P > 0.05). Conclusions: There was no long-term effect of LF19 on any diagnosed allergic disease, airway inflammation or IgE sensitization. This suggests delayed eczema onset but to fully examine long-term benefits a larger study population had been needed. The increase in allergic disease has been attributed to environmental factors including disturbances in early gut colonization patterns (1, 2) and reduced gut microbial diversity (3–5) preceeding the development of allergic disease. With the recognized role of gut microbiota in immune development and regulation (6, 7), there has been interest in shaping gut micro- biota establishment with probiotics. Probiotics may, directly or indirectly, modulate the developing immune system and have been variously shown to have immune-stimulating effects (8). While both antenatal and postnatal factors may influence susceptibility to immune dysregulation (1), oral tolerance is established in the gut postnatally (9). The gut-associated lym- phoid tissue (GALT) accounts for about 70% of the immune system, reflecting the huge immunological challenge conferred by the intestinal luminal contents. Gut microbiota are pro- posed to convey immune-regulating effects via complex path- ways within and further than the GALT (6, 7, 9). During weaning, the maturing mucosal immune system is exposed to an increasing array of dietary antigens and a more complex gut microbiota. Therefore, we hypothesized that feeding the probi- otic Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning could be an effective tool in primary prevention of allergic disease. In our previous reports, LF19 reduced the risk of infant eczema (10) in conjunction with effects on adaptive Allergy 68 (2013) 1015–1020 © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1015 Allergy