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 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. 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. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics 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 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 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 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 Background Prevalence of  allergic diseases in infants , whose parents and siblings do not have allergy , is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative . Intestinal microbiota may modulate immunologic and inflammatory systemic responses and , thus , influence development of sensitization and allergy . Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations about the use of probiotics in the prevention of allergy . Methods We identified the most relevant clinical questions and performed a systematic review of r and omized controlled trials of probiotics for the prevention of allergy . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . We search ed for and review ed the evidence about health effects , patient values and preferences , and re source use ( up to November 2014 ) . We followed the GRADE evidence -to-decision framework to develop recommendations . Results Currently available evidence does not indicate that probiotic supplementation  reduces the risk of developing allergy in children . However , considering all critical outcomes in this context , the WAO guideline panel determined that there is a likely net benefit from using probiotics result ing primarily from prevention of eczema . The WAO guideline panel suggests : a ) using probiotics in pregnant women at high risk for having an allergic child ; b ) using probiotics in women who breastfeed infants at high risk of developing allergy ; and c ) using probiotics in infants at high risk of developing allergy . All recommendations are conditional and supported by very low quality evidence . Conclusions WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding , and whether to give them to infants 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: It is also linked to the recently published WAO guidelines ( 3 ) which are partially conflicting with the previous conclusion because it suggests that ‘ using probiotics in women who breastfeed infants at high risk of developing allergy , because considering all critical outcomes , there is a net benefit result ing primarily from prevention of eczema ( conditional recommendation , very low quality evidence ) ’ .
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