Early markers of allergic disease in a primary prevention study using probiotics: 2.5-year follow-up phase.

BACKGROUND: We previously reported that a Lactobacillus acidophilus probiotic strain (LAFTI) L10/LAVRI-A1) given for the first 6 months of life increased the risk of allergen sensitization at 1 year of age. METHODS: To assess the effects on subsequent allergic outcomes, 153 children from the initial prevention cohort (n = 178) were reviewed at 2.5 years of age. Clinical outcomes were assessed in relation to (i) probiotic supplementation; and (ii) immune function previously assessed at 6 months of age. RESULTS: Supplementation with this probiotic did not reduce the risk of dermatitis at 2.5 years (31/74, 42%) compared with that in placebo group (25/76, 34%). There was no significant reduction in any other allergic disease or allergen sensitization. Inhalant sensitization at 2.5 years (n = 29) was associated with higher proportions of circulating CD4+ CD25+ regulatory T-cell populations (P = 0.005) and higher allergen-induced FOXP3 levels (P = 0.003) at 6 months. This was also seen in children with dermatitis. Children with dermatitis at 2.5 years also had significantly lower toll-like receptor 4 lipopolysaccharide responses at 6 months of age (IL-12 P = 0.04, IL-6 P = 0.039) and lower polyclonal (PHA) responses (IFN-gamma P = 0.005, IL-10 P = 0.001, and IL-6 P = 0.001). Children who had previously received the probiotic had fewer gastrointestinal infections in the preceding 18 months (P = 0.023). CONCLUSION: The LAFTI L10 probiotic strain did not have any significant effect on allergy outcomes. Allergic children showed a number of early differences in immune function including altered regulatory T-cell markers and innate immune function.

Evaluation of the effects of probiotic supplementation from the neonatal period on innate immune development in infancy.

BACKGROUND: Activation of the innate immune system by microbial stimulation is believed to be critical for normal immune maturation, and there has been speculation that these pathways are important for inhibiting allergic-immune responses. OBJECTIVE: To assess innate immune function following a 6-month supplementation with probiotic bacteria. METHODS: Two hundred and thirty-one allergic, pregnant women were recruited into a randomized, controlled trial. The infants received either a probiotic (Lactobacillus acidophilus LAVRI-A1; Probiomics) or placebo (maltodextrin alone) daily for the first 6 months of life. Mononuclear cell samples were available from 118 infants. Functional responses to toll-like receptor (TLR) were assessed using ligands for TLR2 (Pansorbin) and TLR4/CD14 [lipopolysaccharide (LPS)] and measuring cytokine responses in the supernatants. Antigen-presenting cell function, as well as capacity for cytokine production (IL-12p70 and IL-10) was assessed. RESULTS: Infants in the probiotic group did not demonstrate differences in innate immune function compared with those in the control group. No differences were seen when cytokine responses were examined following stimulation with Pansorbin (TLR2) or LPS (TLR4). Similarly, no differences were seen in the antigen-presenting capacity of these infants. The mean fluorescence intensities of human leucocyte antigen-DR (HLA-DR) on monocytes, B cells and dendritic cells (DC) subsets were not affected, nor were the percentage of circulating DC subsets affected by a 6-month supplementation with L. acidophilus LAVRI-A1. CONCLUSIONS: Probiotic supplementation with L. acidophilus for the first 6 months of life did not alter early innate immune responses in this population at high risk of developing allergic disease.

Effects of probiotic supplementation for the first 6 months of life on allergen- and vaccine-specific immune responses.

BACKGROUND: A reduction in microbial burden during infancy when allergen-specific memory is evolving has become a prominent explanation for the allergy epidemic. OBJECTIVE: We sought to determine whether probiotic dietary supplementation in the first 6 months of life could modify allergen- and vaccine-specific immune responses. METHODS: Two hundred and thirty-one pregnant women with a history of allergic disease and positive allergen skin prick test (SPT) were recruited into a randomized-controlled trial. The infants received either a probiotic (3 x 10(9)Lactobacillus acidophilus LAVRI-A1; Probiomics) or placebo (maltodextrin alone) daily for the first 6 months of life, given independent of feeding methods. One hundred and seventy-eight children completed the study; blood samples were available from 60 children in the placebo group and 58 children in the probiotic group. Infant cytokine (IL-5, IL-6, IL-10, IL-13, TNF-alpha or TGF-beta) responses to tetanus toxoid (TT), house dust mite (HDM), ovalbumin (OVA), beta-lactoglobulin (BLG), Staphylococcus enterotoxin B (SEB) and phytohaemaglutinin (PHA) were measured at 6 months of age. RESULTS: Children who received the probiotics showed reduced production of IL-5 and TGF-beta in response to polyclonal (SEB) stimulation (P=0.044 and 0.015, respectively). They also demonstrated significantly lower IL-10 responses to TT vaccine antigen compared with the placebo group (P=0.03), and this was not due to any differences in vaccination. However, there were no significant effects of probiotics on either Type 1 (Th1) or Type 2 (Th2) T helper cell responses to allergens or other stimuli. The only other effects observed were for reduced TNF-alpha and IL-10 responsiveness to HDM allergens in children receiving probiotics (P=0.046 and 0.014, respectively). CONCLUSIONS: In summary, although we did not see any consistent effects on allergen-specific responses, our study suggests that probiotics may have immunomodulatory effects on vaccine responses. The significance and clinical relevance of this need to be determined in further studies.