title: Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial Probiotics during weaning reduce the incidence of eczema. Diversity of the gut microbiota and eczema in early life Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. Maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of eczema in the infant. Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy. Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics for Primary Prevention: No Clinical Effects of Lactobacillus GG Supplementation Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema prevalence to 6 years: does it also reduce atopic sensitization?
abstract: The immunological composition of breast milk differs between mothers . The reasons for these differences and the consequences for the breast-fed infants are poorly understood . The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and  eczema in the babies .  Total IgA , secretory IgA ( SIgA ) , TGF-beta1 , TGF-beta2 , IL-10 , TNF , soluble CD14 ( sCD14 ) , and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri ( n = 54 ) or placebo ( n = 55 ) from gestational week 36 until delivery . Bacteriological analyses of L. reuteri were performed in faecal sample s of the mothers . The infants were followed prospect ively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and /or circulating allergen-specific IgE antibodies at 6 , 12 , and 24 months of age . Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum . For TGF-beta2 , this association was most pronounced in mothers with detectable L. reuteri in faeces . Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life . A similar trend was observed for development of IgE-associated eczema . The levels of total IgA , SIgA , TGF-beta1 , TNF , sCD14 , and Na/K ratios in breast milk were not affected by the intake of L. reuteri . None of these parameters correlated with sensitization or development of eczema in the infant , except for high Na/K ratios that associated with increased risk of sensitization . Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2 , and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants BACKGROUND 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 ) . METHODS In a double-blind , r and omised 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 . FINDINGS  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 ) . INTERPRETATIONS 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 A reduced microbial load early in life has been suggested to be linked to the increasing prevalence of allergic diseases in the industrialized world . Some studies have indicated that probiotics may be effective in the prevention of eczema . In vitro studies indicate that probiotics have immunomodulatory effects . In the present study , we evaluated the effects of feeding Lactobacillus F19 during weaning on the incidence of eczema and Th1/Th2 balance . In a double-blind , placebo-controlled r and omized intervention trial , infants were fed cereals with ( n = 89 ) or without Lactobacillus F19 ( n = 90 ) from 4 to 13 months of age . We assessed the cumulative incidence of eczema at 13 months of age . The ratio of interferon-gamma ( IFN-gamma ) to interleukin 4 ( IL4 ) mRNA expression levels in polyclonally stimulated peripheral blood T cells was used as a proxy for immune balance . Total and specific IgE serum levels were also assessed . The cumulative incidence of eczema at 13 months was 11 % ( 4 - 17 % , 95 % CI ) and 22 % ( 13 - 31 % , 95 % CI ) in the probiotic and placebo groups , respectively ( p < 0.05 ) . The number needed to treat was 9 ( 6.5 - 11.5 , 95 % CI ) . At 13 months of age , the IFN-gamma/IL4 mRNA ratio was higher in the probiotic compared with the placebo group ( p < 0.05 ) . In contrast , there were no differences between groups in serum concentrations of IgE. In summary , feeding Lactobacillus F19 during weaning could be an effective tool in the prevention of early manifestation of allergy , e.g. , eczema . The higher Th1/Th2 ratio in the probiotic compared with the placebo group suggests enhancing effects of Lactobacillus F19 on the T cell-mediated immune response Background A modest number of prospect i ve studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results . Objective To examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture . Methods Fecal sample s were collected from 21 infants at 1 and 4 months of life . Nine infants were diagnosed with eczema by the age of 6 months ( cases ) and 12 infants were not ( controls ) . After conducting denaturating gradient gel electrophoresis ( DGGE ) of stool sample s , we compared the microbial diversity of cases and controls using the number of electrophoretic b and s and the Shannon index of diversity ( H ' ) as indicators . Results Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 ( mean H ' for controls = 0.75 vs. 0.53 for cases , P = 0.01 ) and 4 months ( mean H ' for controls = 0.92 vs. 0.59 for cases , P = 0.02 ) . The increase in diversity from 1 to 4 months of age was significant in controls ( P = 0.04 ) but not in children who developed eczema by 6 months of age ( P = 0.32 ) . Conclusion Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life Controversy exists regarding the preventive effect of probiotics on the development of  eczema or atopic dermatitis .  We investigated whether supplementation of probiotics prevents the development of  eczema in infants at high risk . In a r and omized , double-blind , placebo-controlled trial , 112 pregnant women with a family history of allergic diseases received a once-daily supplement , either a mixture of Bifidobacterium bifidum BGN4 , B. lactis AD011 , and Lactobacillus acidophilus AD031 , or placebo , starting at 4 - 8 wks before delivery and continuing until 6 months after delivery . Infants were exclusively breast-fed during the first 3 months , and were subsequently fed with breastmilk or cow 's milk formula from 4 to 6 months of age . Clinical symptoms of the infants were monitored until 1 yr of age , when the total and specific IgE against common food allergens were measured . A total of 68 infants completed the study . The prevalence of eczema at 1 yr in the probiotic group was significantly lower than in the placebo group ( 18.2 % vs. 40.0 % , p=0.048 ) . The cumulative incidence of eczema during the first 12 months was reduced significantly in probiotic group ( 36.4 % vs. 62.9 % , p=0.029 ) ; however , there was no difference in serum total IgE level or the sensitization against food allergens between the two groups . Prenatal and postnatal supplementation with a mixture of B. bifidum BGN4 , B. lactis AD011 , and L. acidophilus AD031 is an effective approach in preventing the development of eczema in infants at high risk of allergy during the first year of life Using a double blind r and omized placebo‐controlled trial ( Australian New Zeal and Clinical Trials Registry : ACTRN12607000518460 ) , we have shown that in a high risk birth cohort , maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus HN001 ( HN001 ) ( 6 × 109 cfu/day ) halved the cumulative prevalence of eczema by age 2 years . Bifidobacterium animalis subsp lactis HN019 ( HN019 ) ( 9 × 109 cfu/day ) had no effect BACKGROUND An altered microbial exposure may underlie the increase of allergic diseases in affluent societies .  Probiotics may alleviate and even prevent eczema in infants . OBJECTIVE To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri . METHODS Double-blind , r and omized , placebo-controlled trial , which comprised 232 families with allergic disease , of whom 188 completed the study . The mothers received L reuteri ATCC 55730 ( 1 x 10(8 ) colony forming units ) daily from gestational week 36 until delivery . Their babies then continued with the same product from birth until 12 months of age and were followed up for another year . Primary outcome was allergic disease , with or without positive skin prick test or circulating IgE to food allergens . RESULTS The cumulative incidence of eczema was similar , 36 % in the treated versus 34 % in the placebo group . The L reuteri group had less IgE-associated eczema during the second year , 8 % versus 20 % ( P = .02 ) , however . Skin prick test reactivity was also less common in the treated than in the placebo group , significantly so for infants with mothers with allergies , 14 % versus 31 % ( P = .02 ) . Wheeze and other potentially allergic diseases were not affected . CONCLUSION Although a preventive effect of probiotics on infant eczema was not confirmed , the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease . CLINICAL IMPLICATION Probiotics may reduce the incidence of IgE-associated eczema in infancy BACKGROUND Probiotics have shown promising potential in reducing the risk of eczema in infants . Optimal probiotic intervention regimen remains to be determined . OBJECTIVE We investigated whether maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of developing eczema in high-risk infants . METHODS This was a parallel , double-blind placebo-controlled trial of 241 mother-infant pairs . Mothers with allergic disease and atopic sensitization were r and omly assigned to receive ( 1 ) Lactobacillus rhamnosus LPR and Bifidobacterium longum BL999 ( LPR+BL999 ) , ( 2 ) L paracasei ST11 and B longum BL999 ( ST11+BL999 ) , or ( 3 ) placebo , beginning 2 months before delivery and during the first 2 months of breast-feeding . The infants were followed until the age of 24 months . Skin prick tests were performed at the ages of 6 , 12 , and 24 months . RESULTS Altogether 205 infants completed the follow-up and were included in the analyses . The risk of developing eczema during the first 24 months of life was significantly reduced in infants of mothers receiving LPR+BL999 ( odds ratio [ OR ] , 0.17 ; 95 % CI , 0.08 - 0.35 ; P < .001 ) and ST11+BL999 ( OR , 0.16 ; 95 % CI , 0.08 - 0.35 ; P < .001 ) . The respective ORs for chronically persistent eczema were 0.30 ( 95 % CI , 0.12 - 0.80 ; P = .016 ) and 0.17 ( 95 % CI , 0.05 - 0.56 ; P = .003 ) . Probiotics had no effect on the risk of atopic sensitization in the infants . No adverse effects were related to the use of probiotics . CONCLUSION Prevention regimen with specific probiotics administered to the pregnant and breast-feeding mother , that is , prenatally and postnatally , is safe and effective in reducing the risk of eczema in infants with allergic mothers positive for skin prick test To cite this article : Boyle RJ , Ismail IH , Kivivuori S , Licciardi PV , Robins‐Browne RM , Mah L‐J , Axelrad C , Moore S , Donath S , Carlin JB , Lahtinen SJ , Tang MLK . Lactobacillus GG treatment during pregnancy for the prevention of eczema  : a r and omized controlled trial . Allergy 2011 ; 66 : 509–516 BACKGROUND The role of probiotics in prevention of allergic disease is still not clearly established , although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years . OBJECTIVE To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years . METHODS Double-blind , r and omized placebo-controlled trial of infants at risk of allergic disease . Pregnant women were r and omized to take Lactobacillus rhamnosus HN001 ( L rhamnosus ) , Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding , and their infants were r and omized to receive the same treatment from birth to 2 years ( n = 474 ) . The infant 's cumulative prevalence of eczema and point prevalence of atopy , using skin prick tests to common allergens , was assessed at 2 years . RESULTS Infants receiving L rhamnosus had a significantly ( P = .01 ) reduced risk of eczema ( hazard ratio [ HR ] , 0.51 ; 95 % CI , 0.30 - 0.85 ) compared with placebo , but this was not the case for B animalis subsp lactis ( HR , 0.90 ; 95 % CI , 0.58 - 1.41 ) . There was no significant effect of L rhamnosus ( HR , 0.74 ; 95 % CI , 0.46 - 1.18 ) or B animalis subsp lactis ( HR , 0.82 ; 95 % CI , 0.52 - 1.28 ) on atopy . L rhamnosus ( 71.5 % ) was more likely than B animalis subsp lactis ( 22.6 % ) to be present in the feces at 3 months , although detection rates were similar by 24 months . CONCLUSION We found that supplementation with L rhamnosus , but not B animalis subsp lactis , substantially reduced the cumulative prevalence of eczema , but not atopy , by 2 years . Underst and ing how Lactobacilli act to prevent eczema requires further investigation BACKGROUND Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy . This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age . OBJECTIVE To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects . METHODS A r and omized , placebo-controlled trial with oral supplementation with L. reuteri ATCC 55730 ( 1 × 10(8 ) CFU ) during the last month of gestation and through the first year of life comprising 232 families with allergic disease , of whom 184 completed a 7-yr follow-up . The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity ( Clinical Trials.gov ID NCT01285830 ) . RESULTS The prevalence of asthma ( 15 % in the probiotic vs. 16 % in placebo group ) , allergic rhinoconjunctivitis ( 27 % vs. 20 % ) , eczema ( 21 % vs. 19 % ) and skin prick test reactivity ( 29 % vs. 26 % ) was similar in the probiotic and placebo group . Growth indices and gastrointestinal symptoms were similar in the two groups . No severe adverse events were reported . CONCLUSION The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age . Thus , the effect of L. reuteri on the immune system seems to be transient . Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects BACKGROUND . The value of probiotics for primary prevention is controversial . Published trials vary considerably in study design and the applied probiotics , thereby limiting comparability of the results . OBJECTIVE . The purpose of this trial was to study the preventive effect of the probiotic Lactobacillus GG on the development of atopic dermatitis . METHODS . In a double-blind , placebo-controlled prospect i ve trial , 105 pregnant women from families with ≥1 member ( mother , father , or child ) with an atopic disease were r and omly assigned to receive either the probiotic Lactobacillus GG ( American Type Culture Collection 53103 ; 5 × 109 colony-forming units of Lactobacillus GG twice daily ) or placebo .  Ninety-four families ( 89.5 % ) completed the trial . The supplementation period started 4 to 6 weeks before expected delivery , followed by a postnatal period of 6 months . The primary end point was the occurrence of atopic dermatitis at the age of 2 years . Secondary outcomes were severity of atopic dermatitis , recurrent episodes of wheezing bronchitis , and allergic sensitization at the age of 2 years . RESULTS . Atopic dermatitis was diagnosed in 14 ( 28 % ) of 50 in the Lactobacillus GG group and in 12 ( 27.3 % ) of 44 in the placebo group . The risk of atopic dermatitis in children on probiotics relative to placebo was 0.96 ( confidence interval 0.38–2.33 ) . Severity of atopic dermatitis was comparable between the 2 groups . Notably , children with recurrent ( ≥5 ) episodes of wheezing bronchitis were more frequent in the Lactobacillus GG group ( 26 % ; n = 13 ) , as compared with the placebo group ( 9.1 % ; n = 4 ) . No difference was observed between both groups in total immunoglobulin E concentrations or numbers of specific sensitization to inhalant allergens . CONCLUSIONS . Supplementation with Lactobacillus GG during pregnancy and early infancy neither reduced the incidence of atopic dermatitis nor altered the severity of atopic dermatitis in affected children but was associated with an increased rate of recurrent episodes of wheezing bronchitis . Therefore , Lactobacillus GG can not be generally recommended for primary 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 The role of probiotics in prevention of  allergic disease  is still not clear ; efficacy may depend on the timing , dose , duration , and specific probiotic used . Using a double‐blind r and omized placebo‐controlled trial ( Australian New Zeal and Clinical Trials Registry : ACTRN12607000518460 ) , we have shown that in a high‐risk birth cohort , maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation from birth until 2 years with Lactobacillus rhamnosus HN001 ( HN001 ) ( 6 × 109 cfu/day ) halved the cumulative prevalence of eczema at 2 and 4 years . Bifidobacterium animalis subsp lactis HN019 ( HN019 ) ( 9 × 109 cfu/day ) had no significant effect
target: The results of the present meta- analysis show that probiotic supplementation  prevents infantile eczema , thus suggesting a new potential indication for probiotic use in pregnancy and infancy
background: Growing evidence underlines the pivotal role of infant gut colonization in the development of the immune system .
  The possibility to modify gut colonization through probiotic supplementation in childhood might prevent atopic diseases .
  The aim of the present systematic review and meta- analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing atopic diseases .