ORIGINAL ARTICLE Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial A Singh 1 , F Hacini-Rachinel 1,4 , ML Gosoniu 2 , T Bourdeau 1 , S Holvoet 1 , R Doucet-Ladeveze 1 , M Beaumont 3 , A Mercenier 1 and S Nutten 1 BACKGROUND/OBJECTIVES: Probiotics are defined as ‘living micro-organisms that when administered in adequate amounts confer a health benefit to the host’. Different probiotic strains have been investigated for beneficial effects on allergic disorders. The purpose of the current study was to evaluate the effect of orally administering the probiotic Nestle ´ culture collection (NCC)2818 Bifidobacterium lactis strain on immune parameters and nasal symptom scores in subjects suffering from seasonal allergic rhinitis (SAR). SUBJECTS/METHODS: The study was a double-blinded, parallel, randomized placebo-controlled trial conducted during the peak of the pollen season. Adult subjects with clinical history of SAR and positive skin prick test to grass pollen were recruited. The subjects received B. lactis NCC2818 or placebo for 8 weeks and completed symptom questionnaires every week. Whole blood was collected at baseline (V1), 4 weeks (V2) and 8 weeks (V3) to measure immune parameters. RESULTS: Concentrations of Th-2 cytokines, secreted by stimulated blood lymphocytes, were significantly lower in the probiotic group compared with the placebo group at V3 (interleukin (IL)-5, P ¼ 0.016; IL-13, P ¼ 0.005). Total nasal symptom scores were significantly lower in the second month of the study (weeks 5–8) in the probiotic group compared with the placebo group (P ¼ 0.03). Also, percentages of activated CD63 expressing basophils were significantly lower in the probiotic group at V2 (P ¼ 0.02). CONCLUSIONS: Oral administration of the probiotic NCC2818 mitigates immune parameters and allergic symptoms during seasonal exposure. These promising results warrant that B. lactis NCC2818 be investigated further in large-scale trials for management of respiratory allergy. European Journal of Clinical Nutrition (2013) 67, 161–167; doi:10.1038/ejcn.2012.197; published online 9 January 2013 Keywords: probiotic; seasonal allergic rhinitis; IL-5; IL-13; total nasal symptom score INTRODUCTION Allergic rhinitis (AR) is of two types, seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR), in which symptoms last throughout the year. 1,2 Management of AR requires avoidance of the causative allergen, treatment of the nasal symptoms with anti- histamines and corticosteroids, and in some cases allergen- specific immunotherapy. Intranasal corticosteroids are considered the gold standard approach to manage symptoms of AR. While they are effective in short term, many of the associated symptoms such as nasal congestion remain unaffected. 3,4 Recently, nutritional interventions with probiotics have been investigated for their beneficial effects on allergic disorders. Probiotics are defined by the WHO as ‘living micro-organisms that when administered in adequate amounts confer a health benefit to the host’. 5 The ability of certain probiotic strains to modulate the immune system is currently an area of intense research. 6–8 The beneficial roles of probiotics, especially of the genera Lactobacillus and Bifidobacterium, in allergic diseases have been investigated with increasing interest in animal models and human clinical trials 9–11 where probiotics are sought to influence the gut microbiota composition and restore homeostasis of the host immune system. 12,13 Several probiotic strains have previously been evaluated for their effect in AR. 14–20 Lactobacillus casei Shirota strain has been demonstrated to impact the immune system and allergic symptoms 14,16 while Lactobacillus plantarum strains have been shown to inhibit allergic cytokines. 15 In another study, Bifidobacterium longum BB536 strain alleviated symptoms of SAR. 19–21 Studies with different Lactobacillus paracasei strains have shown potential for both SAR 18 and PAR. 17 In the current study, we have sought to examine the effect of oral administration of the Bifidobacterium lactis NCC2818 strain in reducing immune markers and alleviating allergic symptoms in subjects suffering from SAR to grass pollen (GP). Previous clinical studies on atopic 1 Allergy Group, Department of Nutrition and Health, Nestle ´ Research Center, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, Switzerland; 2 Biostatistics Group, Clinical Developmental Unit, Vers-chez-les-Blanc, Lausanne, Switzerland and 3 Clinical Evaluation Group, Department of Bio-Analytical Science, Nestle ´ Research Center, Vers-chez-les-Blanc, Lausanne, Switzerland. Correspondence: Dr A Singh, Allergy Group, Department of Nutrition and Health, Nestle ´ Research Center, Nestec Ltd, Vers-chez-les-Blanc, CH-1000, Lausanne 26, Switzerland. E-mail: anurag.singh@rdls.nestle.com Contributors: AS, FH-R, MB, AM and SN designed the research; AS, FH-R, TB, SH, RDL and MB conducted the research; AS, FH-R, TB, SH, RDL and MLG analyzed the data; and AS, MLG, AM and SN wrote the final paper. All authors read and approved the final manuscript. 4 Current address: Galderma R&D, Route des Colles- Sophia Antipolis, Biot, France. Received 22 August 2012; revised 2 November 2012; accepted 7 November 2012; published online 9 January 2013 European Journal of Clinical Nutrition (2013) 67, 161–167 & 2013 Macmillan Publishers Limited All rights reserved 0954-3007/13 www.nature.com/ejcn