Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Probiotics in the management of atopic eczema. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial.
The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system. Probiotics, live health-promoting microbes, might offer such stimulation.
                We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases.
                We randomized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery. Their infants received the same probiotics plus galacto-oligosaccharides (n = 461) or a placebo (n = 464) for 6 months. At 2 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, and allergic rhinitis) and IgE sensitization (positive skin prick test response or serum antigen-specific IgE level >0.7 kU/L). Fecal bacteria were analyzed during treatment and at age 2 years.
                Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated (atopic) diseases (odds ratio [OR], 0.71; 95% CI, 0.50-1.00; P = .052). Probiotic treatment reduced eczema (OR, 0.74; 95% CI, 0.55-0.98; P = .035) and atopic eczema (OR, 0.66; 95% CI, 0.46-0.95; P = .025). Lactobacilli and bifidobacteria more frequently (P < .001) colonized the guts of supplemented infants.
                Probiotic treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema. The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics.
                The prevention of atopic eczema in high-risk infants is possible by modulating the infant's gut microbiota with probiotics and prebiotics. Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult.
                To assess the effect of supplementation of an infant and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life.
                Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group).
                A total of 414 infants were randomized to the prebiotic group and 416 infants to the control group. A total of 300 infants were followed in the breast-feeding group. Up to the first birthday, atopic dermatitis occurred in significantly fewer infants from the prebiotic group (5.7%) than from the control group (9.7%; P = .04). The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group (7.3%). In a Cox regression model, the rate of atopic dermatitis was significantly lower by 44% in the prebiotic group versus the control group (P = .04). The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants.
                Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.
                Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora.
                To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis (AD) during the first six months of life in formula fed infants at high risk of atopy.
                Prospective, double-blind, randomised, placebo controlled trial; 259 infants at risk for atopy were enrolled. A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study. If bottle feeding was started, the infant was randomly assigned to one of two hydrolysed protein formula groups (0.8 g/100 ml prebiotics or maltodextrine as placebo). All infants were examined for clinical evidence of atopic dermatitis. In a subgroup of 98 infants, faecal flora was analysed.
                Ten infants (9.8%; 95 CI 5.4-17.1%) in the intervention group and 24 infants (23.1%; 95 CI 16.0-32.1%) in the control group developed AD. The severity of the dermatitis was not affected by diet. Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts.
                Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants. Although the mechanism of this effect requires further investigation, it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy. Despite preliminary evidence, the role of probiotics in allergy prevention is unclear.
                To determine whether early probiotic supplementation prevents allergic disease in high-risk infants.
                Newborns of women with allergy (n = 231) received either Lactobacillus acidophilus (LAVRI-A1) or placebo daily for the first 6 months of life. Children were assessed for atopic dermatitis (AD) and other symptoms at 6 and 12 months and had allergen skin prick tests (SPT) at 12 months of age.
                A total of 178 infants completed the supplementation period. Those in the probiotic group showed significantly higher rates of Lactobacillus colonization (P = .039). At 6 months, AD rates were similar in the probiotic (n = 23/89; 25.8%) and placebo (n = 20/88; 22.7%) groups (P = .629). There was also no difference at 12 months, although the proportion of children with SPT+AD was significantly higher in the probiotic group (P = .045). At 12 months, the rate of sensitization was significantly higher in the probiotic group (P = .030). The presence of culturable Lactobacilli or Bifidobacterium in stools in the first month of life was not associated with the risk of subsequent sensitization or disease; however, the presence of Lactobacillus at 6 months of age was associated with increased risk of subsequent cow's milk sensitization (P = .012).
                Early probiotic supplementation with L acidophilus did not reduce the risk of AD in high-risk infants and was associated with increased allergen sensitization in infants receiving supplements. The long-term significance of the increased rate of sensitization needs to be investigated in further studies.
                These findings challenge the role of probiotics in allergy prevention. The prevalence of atopic diseases is increasing throughout the Western world, and means of primary prevention are needed to reverse this trend. The role of breast-feeding, the best source of infant nutrition, in protection against atopic disease remains elusive. In this double-blinded, placebo-controlled study of 62 mother-infant pairs, it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk, as assessed by the amount of anti-inflammatory transforming growth factor beta2 (TGF-beta2) in the milk (2885 pg/mL [95% CI, 1624-4146] in mothers receiving probiotics vs 1340 pg/mL [95% CI, 978-1702] in mothers receiving placebo; P =.018). The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo (15% and 47%, respectively; relative risk, 0.32 [95% CI, 0.12-0.85]; P =.0098). Maternal atopy was a clear risk factor for atopic eczema in the infant. The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration. Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life. Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS.
                Follow-up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double-blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120 infants.
                In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE-sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, -26.1 vs-19.8 (P=0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE-sensitized subgroup.
                Treatment with LGG may alleviate AEDS symptoms in IgE-sensitized infants but not in non-IgE-sensitized infants. Over the last two decades the incidence of allergic diseases has increased in industrialized countries, and consequently new approaches have to be explored.
                The potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study.
                A total of 27 infants, mean age 4.6 months, who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented, Bifidobacterium lactis Bb-12 or Lactobacillus strain GG (ATCC 53103), extensively hydrolysed whey formulas or to the same formula without probiotics. The extent and severity of atopic eczema, the growth and nutrition of infants, and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined.
                The SCORAD score reflecting the extent and severity of atopic eczema was 16 (7-25) during breast-feeding, median (interquartile range). After 2 months, a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas, as compared to the unsupplemented group; chi(2) = 12.27, P = 0.002. SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 (0-3.8), and in the Lactobacillus GG group to 1 (0.1-8.7), vs unsupplemented 13.4 (4.5-18.2), median (interquartile range), in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine.
                The results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation. The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu. The combined effects of these probiotic strains will guide infants through the weaning period, when sensitization to newly encountered antigens is initiated. The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies. Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy).
                In a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint.
                Atopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0.51 [95% CI 0.32-0.84]). The number needed to treat was 4.5 (95% CI 2.6-15.6).
                Lactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease. Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD).
                The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy.
                We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation.
                No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA.
                We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.
Further research is needed before routine use of prebiotics can be recommended for prevention of allergy in formula fed infants. There is some evidence that a prebiotic supplement added to infant feeds may prevent eczema. It is unclear whether the use of prebiotic should be restricted to infants at high risk of allergy or may have an effect in low risk populations; or whether it may have an effect on other allergic diseases including asthma.