FOXP3 mRNA expression at 6 months of age is higher in infants who develop atopic dermatitis, but is not affected by giving probiotics from birth. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features Early differences in fecal microbiota composition in children may predict overweight. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial Lactobacillus casei Abundance Is Associated with Profound Shifts in the Infant Gut Microbiome World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics Effect of a New Synbiotic Mixture on Atopic Dermatitis in Children: a Randomized-Controlled Trial Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. Nutritional advantages of probiotics and prebiotics. Probiotics Modulate Host-Microbe Interaction in the Placenta and Fetal Gut: A Randomized, Double-Blind, Placebo-Controlled Trial Effects of Bifidobacterium lactis Bb12 Supplementation on Intestinal Microbiota of Preterm Infants: a Double-Blind, Placebo-Controlled, Randomized Study Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics for Primary Prevention: No Clinical Effects of Lactobacillus GG Supplementation Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines. Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Perinatal probiotic supplementation in the prevention of allergy related disease: 6 year follow up of a randomised controlled trial Factors influencing the infant gut microbiome at age 3‐6 months: Findings from the ethnically diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART) World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics Allergy development and the intestinal microflora during the first year of life. Probiotic Bacteria in the Management of Atopic Disease: Underscoring the Importance of Viability
Factors that influence immune regulation in early life may be implicated in the rise in allergic disease , including reduced microbial burden . The aim of the study was to examine the infant regulatory T-cell function in relation to ( a ) probiotic supplementation for the first 6 months of life and ( b ) the subsequent development of an early allergic phenotype . Two hundred and thirty-one allergic , pregnant women were recruited into a r and omized , controlled trial . The infants received either a probiotic or placebo daily for the first 6 months of life . One hundred and seventy-eight children completed the study , with blood sample s available from 118 ( 60 placebo ; 58 probiotic ) .  CD4(+)CD25(+)CTLA4(+)T-regulatory phenotype and allergen-induced FOXP3 mRNA expression were compared in relation to this intervention as well as according to evidence of early disease ( atopic dermatitis ) . The administration of probiotics was not associated with any significant differences in the proportion of circulating CD4(+)CD25(+)CTLA4(+)cells , or in the resting expression of FOXP3 . There were also no relationships between these parameters and patterns of gut colonization , and this probiotic did not reduce the risk of atopic dermatitis . Children who developed  atopic dermatitis ( n = 36/118 ) had significantly higher induced FOXP3 expression following stimulation with both house dust mite ( HDM ) ( p = 0.017 ) and ovalbumin ( OVA ) allergens ( p = 0.021 ) than those that did not develop atopic dermatitis . Although this relationship was seen in both the probiotic and placebo groups , it was more pronounced in the probiotic group . However , regression analysis demonstrated that higher allergen-induced FOXP3 expression was predicted by the presence of atopic dermatitis ( p = 0.018 ) rather than probiotics supplementation ( p = 0.217 ) . The higher levels of allergen-induced FOXP3 in atopic dermatitis suggest activation of these compensatory mechanisms rather than a primary defect in this pathway . Probiotic supplementation and gut colonization did not appear to substantially modify these regulatory pathways , or the risk of developing atopic dermatitis BACKGROUND 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 . OBJECTIVE We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases . METHODS We r and omized 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 . RESULTS 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 . CONCLUSION 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 . CLINICAL IMPLICATION S The prevention of atopic eczema in high-risk infants is possible by modulating the infant 's gut microbiota with probiotics and prebiotics Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention . However , evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial . We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome . A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage . In colonized , but not germ-free mice , probiotics encountered a marked mucosal colonization resistance . In contrast , humans featured person- , region- and strain-specific mucosal colonization patterns , hallmarked by predictive baseline host and microbiome features , but indistinguishable by probiotics presence in stool . Consequently , probiotics induced a transient , individualized impact on mucosal community structure and gut transcriptome . Collectively , empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa , meriting development of new personalized probiotic approaches BACKGROUND Experimental studies suggest that gut microbiota deviations predispose toward energy storage and obesity . OBJECTIVE We wanted to establish whether early gut microbiota composition can guide weight development throughout early childhood . DESIGN Overweight and obese children ( n = 25 ) were selected from a prospect i ve follow-up study at the age of 7 y and identified according to the International Obesity Task Force criteria . Normal-weight children ( n = 24 ) were selected from the same cohort and matched for gestational age and body mass index at birth , mode of delivery , probiotic supplementation  , duration of breastfeeding , use of antibiotics during infancy , and frequencies of atopic diseases and atopic sensitization . Early fecal microbiota composition was analyzed by fluorescent in situ hybridization ( FISH ) with microscopic and flow cytometry detection and by quantitative real-time polymerase chain reaction ( qRT-PCR ) . RESULTS The bifidobacterial numbers in fecal sample s during infancy , as assessed by the FISH with flow cytometry , were higher in children remaining normal weight , [ median : 2.19 x 10(9 ) cells/g ( interquartile range : 1.10 - 5.28 x 10(9 ) cells/g ) ] than in children becoming overweight [ 1.20 x 10(9 ) cells/g ( 0.48 - 1.59x 10(9 ) cells/g ) ; P = 0.02 ] . A similar tendency was found by FISH with microscopic detection and qRT-PCR . The microbiota aberrancy during infancy in children becoming overweight was also associated with a greater number of Staphylococcus aureus [ 0.64 x 10(6 ) cells/g ( 0.33 - 1.00 x 10(6 ) cells/g ) ] than in children remaining normal weight [ 0.27 x 10(6 ) cells/g ( 0.17 - 0.50 x 10(6 ) cells/g ) ; P = 0.013 ] . CONCLUSION Aberrant compositional development of the gut microbiota precedes overweight , offering new possibilities for preventive and therapeutic applications in weight management 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 Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response . Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of  asthma and atopy in older children . Here we describe high-resolution culture-independent analysis of stool sample s from 6-month old infants fed daily supplements of Lactobacillus casei subsp  . Rhamnosus ( LGG ) or placebo in a double-blind , r and omized Trial of Infant Probiotic Supplementation ( TIPS )  . Bacterial community composition was examined using a high-density microarray , the 16S rRNA PhyloChip , and the microbial assemblages of infants with either high or low LGG abundance were compared . Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species , and were significantly more even in their distribution of community members . Ecologically , these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens . PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy , as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species . From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable , even , and functionally redundant infant gastrointestinal community 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 Objective Atopic dermatitis ( AD ) is the most common chronic relapsing skin disease seen in infancy and childhood . The intestinal microbiota play an important role in immune development and may play a role in the development of allergic disorders . Manipulation of the intestinal microbiota by synbiotics may therefore offer an approach to the prevention or treatment of AD and allergic diseases . We studied the clinical and immunologic effects of a new symbiotic ( a mixture of seven probiotic strains of bacteria and Fructooligosaccharide ) in infants and children with AD . Methods In a r and omized , double-blind , placebo-controlled study , 40 infants and children aged 3 months to 6 years with AD received either a synbiotic or placebo for 8 weeks . The Severity Scoring of Atopic Dermatitis ( SCORAD ) index was recorded at baseline and also at 4 and 8 weeks of treatment . Findings There was no significant difference between the probiotic and placebo group in baseline characteristics including sex , age , family history , corticosteroid usage and prick testing . Mean age was 23 months . The synbiotic group showed a significantly greater reduction in SCORAD than did the placebo group ( P=0.001 ) . No specific effect was demonstrated of the probiotics employed on cytokine profile ( P=0.4 , P=0.6 ) . Egg white was the most common ( 45 % ) allergen followed by peanut and cow 's milk . Conclusion This study provides evidence that a mixture of seven strains of probiotics and Fructooligosaccharide can clinical ly improve the severity of  AD in young children . Further studies are needed to investigate the effects on underlying immune responses and the potential long term benefits for patients with AD The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 ( HIV-1 ) infection to the Acquired Immunodeficiency Syndrome ( AIDS ) was proposed in 1995 . Over the last five years , new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue ( GALT ) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS . Current studies show that loss of gut CD4 + Th17 cells , which differentiate in response to normal microflora , occurs early in HIV-1 disease . Microbial translocation and suppression of the T regulatory ( Treg ) cell response is associated with chronic immune activation and inflammation . Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS . Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens , reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation . The interaction of chronic or recurrent infections , and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child . While effective anti-retroviral therapy ( ART ) has enhanced survival , wasting is still an independent predictor of survival and a major presenting symptom . Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants . Nutritional intervention after 6 months of age appears to be largely ineffective . A meta analysis of r and omized , controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to formula alone . Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4 + T cells . The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many setting s including HIV-1 infection . As discussed here , current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection . Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection . Probiotic bacteria may stabilize CD4 + T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system BACKGROUND : Eczema is the most common inflammatory skin disease of childhood , characterized by an itchy red rash that usually involves the face and skin folds . There is currently no curative treatment for eczema , so the reduction of eczema incidence through disease prevention is a desirable goal . Potential interventions for preventing eczema include exclusive breastfeeding , hydrolysed protein formulas and soy formulas when bottle feeding , maternal antigen avoidance , omega oil supplementation , prebiotics and probiotics . OBJECTIVES : This overview of review s aims to present the current body of data from Cochrane and non-Cochrane review s to provide the most up-to- date evidence on the efficacy and safety of interventions to prevent eczema in infants and children at different risk levels for developing allergic disease . METHODS : Our pool of Cochrane and non-Cochrane review s came from the 2010 United Kingdom National Health Service ( NHS ) Evidence Skin Disorders Annual Evidence Up date s Mapping Exercise on Atopic Eczema . This group used a comprehensive search strategy last conducted in August 2010 to identify all systematic review s on eczema prevention . We identified all review s that met our pre-specified inclusion criteria , and data were extracted , analysed , compiled into tables and synthesized using quantitative and qualitative methods . MAIN RESULTS : Seven systematic review s containing 39 relevant trials with 11 897 participants were included in this overview . Overall , there was no clear evidence that any of the main interventions review ed reduced eczema incidence . In subgroup analyses of infants at high risk of allergic disease , an observational study found that exclusive breastfeeding for at least six months compared with introduction of solids at three to six months decreased the incidence of eczema by 60 % ( risk ratio ( RR ) : 0.40 ; 95 % confidence interval ( CI ) : 0.21 , 0.78 ) , and a r and omized controlled trial found that prebiotics compared with no prebiotics  decreased incidence by 58 % ( RR : 0.42 ; 95 % CI : 0.21 , 0.84 ) . However , each of these findings was based on the results of a single small trial , and no intervention reduced eczema incidence beyond the first two years of life . Although we pre-specified incidence of atopic eczema ( i.e. eczema associated with immunoglobulin E ( IgE ) sensitization ) as a primary outcome , data on whether participants diagnosed with eczema were truly atopic were largely lacking from systematic review s. Similarly , data on atopy , measured using skin prick tests or specific IgE tests to allergens , were not reported in many review s. No interventions were found to decrease atopy when reported . Adverse events data were generally lacking , but data from a trial of probiotics versus no probiotics showed significantly more spitting up in the first one ( RR : 1.88 ; 95 % CI : 1.03 , 3.45 ) and two ( RR : 1.69 ; 95 % CI : 1.02 , 2.80 ) months of life , but no overall increase in risk of gastrointestinal symptoms in the first year . AUTHORS # ENTITYSTARTX02019 ; CONCLUSIONS : Although there is currently no clear evidence showing that any of the interventions examined in this overview prevent eczema in participants not selected for risk of allergic disease , there is some evidence that exclusive breastfeeding for at least six months and prebiotics might reduce eczema incidence in high-risk participants . However , these conclusions are based on limited evidence with method ological shortcomings . Future research on prevention of eczema is needed and should examine different types of hydrolysed formulas , prebiotics and probiotics , as well as enhancement of the skin barrier and other novel approaches in infants at different risk levels for developing allergic disease 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 potential ' nutritional advantages ' of probiotics and prebiotics consist of preventive , and sometimes curative , effects against certain diseases . The evidence supporting such advantages , which requires r and omised controlled trials and consistency of results from study to study , is rapidly increasing . This article summarizes the effects against diseases of intestinal origin . There is a high level of evidence for positive effects of some prebiotics to alleviate  constipation  and treat  hepatic encephalopathy .  Interesting aspects , but with a lower level of evidence at the present time , include prevention of colon cancer , intestinal infection , and recurrence of inflammatory bowel disease . There is a high level of evidence for positive effects of some probiotics in the alleviation of lactose intolerance , antibiotic-associated intestinal disorders and gastroenteritis . Evidence is rapidly growing regarding the prevention of recurrence of inflammatory bowel diseases . Positive trials have suggested preventive effects against intestinal colonization with specific gut pathogens including Clostridium difficile and Helicobacter pylori Background : Early host-microbe interaction provides important maturational stimuli for the developing immune system . The role of prenatal microbial contact remains elusive . Objectives : Our aim was to investigate whether microbes in placenta or amniotic fluid affect fetal innate immune gene expression during late pregnancy and whether innate immune gene expression profiles in the placenta and the fetal gut may be modulated by dietary supplementation with specific probiotics . Methods : Altogether 43 pregnant women were r and omized to receive ( 1 ) Bifidobacterium lactis , ( 2 ) B. lactis in combination with Lactobacillus rhamnosus GG ( LGG ) or ( 3 ) placebo for 14 days before elective cesarian section at full term in a double-blind clinical trial . Bacteria in amniotic fluid and placenta were detected by quantitative (q)PCR . The expression of Toll-like receptor (TLR)-related genes in the placenta and meconium sample s was assessed by qPCR . Gene expression patterns in meconium were interpreted to reflect immune physiology in the fetal gut . Results : The study was completed by 29 mother-infant pairs . Bacterial DNA was detected in all placenta sample s. Microbial DNA in amniotic fluid and placenta was associated with changes in TLR-related gene expression in the fetal intestine . Maternal probiotic supplementation significantly modulated the expression of TLR-related genes both in the placenta and in the fetal gut . Conclusions : Microbial contact in utero is associated with changes in fetal intestinal innate immune gene expression profile . Fetal and placental immune physiology may be modulated by maternal dietary intervention using specific probiotics ABSTRACT The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that of term infants . In particular , the colonization of preterm infants by bifidobacteria is delayed . A double-blind , placebo-controlled , r and omized clinical study was performed on 69 preterm infants to investigate the role of Bifidobacterium lactis Bb12 supplementation in modifying the gut microbiota . Both culture-dependent and culture-independent approaches were used to study the gut microbiota . Bifidobacterial numbers , determined by fluorescence in situ hybridization , were significantly higher in the probiotic than in the placebo group ( log10 values per g of fecal wet weight : probiotic , 8.18 + 0.54 [ st and ard error of the mean ] ; placebo , 4.82 + 0.51 ; P < 0.001 ) . A similar trend for bifidobacterial numbers was also obtained with the culture-dependent method . The infants supplemented with Bb12 also had lower viable counts of Enterobacteriaceae ( log10 values of CFU per g of fecal wet weight : probiotic , 7.80 + 0.34 ; placebo , 9.03 + 0.35 ; P = 0.015 ) and Clostridium spp . ( probiotic , 4.89 + 0.30 ; placebo , 5.99 + 0.32 ; P = 0.014 ) than the infants in the placebo group . Supplementation of B. lactis Bb12 did not reduce the colonization by antibiotic-resistant organisms in the study population . However , the probiotic supplementation increased the cell counts of bifidobacteria and reduced the cell counts of enterobacteria and clostridia 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 Microbial exposure is necessary for the development of normal immune function , which has driven the idea of using probiotics for treatment and prevention of  immune-mediated diseases in infancy and childhood . Mounting evidence indicates that probiotics have immunomodulatory effects . However , the mechanisms are still poorly understood . Specific antibody response is a valuable proxy for immune system maturation status in infancy . We aim ed at determining the impact of Lactobacillus F19 ( LF19 ) during weaning on infections and IgG antibody responses to routine vaccines . In a double-blind , placebo-controlled r and omized intervention trial , infants were fed cereals with ( n = 89 ) or without LF19 ( n = 90 ) from 4 to 13 months of age . Infants were immunized with DTaP ( diphtheria and tetanus toxoid and acellular pertussis ) , polio and Hib-conjugate vaccines at ( 3 ) , 5(1/2 ) and 12 months of age . We assessed the number of days with infections , antibiotic prescriptions and antibody concentrations to Hib capsular polysaccharide ( HibPS ) , diphtheria toxin ( D ) and tetanus toxoid ( T ) before and after the second and third doses . Days with infectious symptoms did not differ between the groups . Days with antibiotic prescriptions were fewer in the LF19 group ( p = 0.044 ) . LF19 enhanced anti-D concentrations when adjusting for breastfeeding duration and colonization with LF19 ( p = 0.024 ) . There was an interaction of the intervention and colonization with LF19 on anti-T concentrations during the course of vaccination ( p = 0.035 ) . The anti-HibPS concentrations were higher after the first and second dose of Hib vaccine in infants breastfed < 6 months compared with those breastfed > or = 6 months ( p < 0.05 ) , with no effect by LF19 . In conclusion , feeding LF19 did not prevent infections , but increased the capacity to raise immune responses to protein antigens , with more pronounced effects in infants breastfed < 6 months Background : Recent data have outlined a relationship between the composition of the intestinal microflora and  allergic inflammation  , and demonstrated the competence of probiotics in downregulation of such inflammation . Aims : Our aims were to characterise the relationship between gut microbes and the extent of allergic sensitisation and to assess whether the efficacy of bifidobacterial supplementation in the treatment of allergy could relate to modulation of the intestinal microbiota . Methods : This r and omised study included 21 infants with early onset atopic eczema of whom eight were intolerant ( highly sensitised group ( HSG ) ) and 13 tolerant ( sensitised group ( SG ) ) to extensively hydrolysed whey formula ( EHF ) .  In the SG , six were weaned to EHF without ( placebo group ( PG ) ) and seven to EHF with Bifidobacterium lactis Bb-12 supplementation ( bifidobacteria treated group ( BbG ) ) . The faecal microflora of infants in the HSG was analysed only before weaning whereas in the SG the faecal microflora was analysed both before and after weaning . Results : Infants in the HSG had greater numbers of lactobacilli/enterococci than those in the SG . Serum total IgE concentration correlated directly with Escherichia coli counts in all infants and with bacteroides counts in the HSG , indicating that the presence of these bacteria is associated with the extent of atopic sensitisation . The effect of supplementation was characterised as a decrease in the numbers of Escherichia coli and protection against an increase in bacteroides numbers during weaning . Conclusions : These data indicate that bifidobacterial supplementation appears to modify the gut microbiota in a manner that may alleviate allergic inflammation . Further studies are needed to confirm this conclusion BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later . Allergic children have a different fecal microflora , with less lactobacilli and bifidobacteria . Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation . OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies . METHODS In a double-blinded , placebo-controlled study we r and omized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture ( 2 lactobacilli , bifidobacteria , and propionibacteria ) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months . Infants also received a prebiotic galacto-oligosaccharide or placebo . At 5 years , we evaluated the cumulative incidence of allergic diseases ( eczema , food allergy , allergic rhinitis , and asthma ) and IgE sensitization . RESULTS Of the 1018 intent-to-treat infants , 891 ( 88 % ) attended the 5-year visit .  Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar : 52.6 % versus 54.9 % and 29.5 % versus 26.6 % , respectively , and 41.3 % in both . No significant difference appeared in frequencies of eczema ( 39.3 % vs 43.3 % ) , atopic eczema ( 24.0 % vs 25.1 % ) , allergic rhinitis ( 20.7 % vs 19.1 % ) , or asthma ( 13.0 % vs 14.1 % ) between groups . However , less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics ( 24.3 % vs 40.5 % ; odds ratio , 0.47 ; 95 % CI , 0.23 % to 0.96 % ; P = .035 ) . CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children . It conferred protection only to cesarean-delivered children Background Perinatal probiotics supplementation has been shown to be effective in the primary prevention of  atopic dermatitis ( AD ) in early childhood , although the long term effects of probiotics on AD and other allergic diseases is less certain . We have previously reported a significant reduction in the cumulative incidence of AD at 2 years after maternal probiotic supplementation . In this study we present the effects of perinatal probiotics given to women from a general population on allergy related diseases in their offspring at 6 years . Methods Four hundred and fifteen pregnant women were r and omised to receive  probiotic or placebo milk  in a double-blinded trial from 36 week gestation until 3 months postpartum . Probiotic milk contained Lactobacillus rhamnosos GG , L. acidophilus La-5 and Bifidobacterium animalis subsp . lactis Bb-12 . At 6 years , children were re-assessed for AD , atopic sensitisation , asthma and allergic rhinoconjunctivitis ( ARC ) . Results At 6 years , 81 and 82 children were assessed for AD in the probiotic and placebo groups , respectively . In a multiple imputation analysis , there was as trend towards a lower cumulative incidence of AD in the probiotic group compared to the placebo group ( OR 0.64 , 95 % CI 0.39 - 1.07 , p = 0.086 ; NNT = 10 ) . This finding was statistically significantly in the complete case analysis ( OR 0.48 , 95 % CI 0.25 - 0.92 , p = 0.027 , NNT = 6 ) . The prevalence of asthma and atopic sensitisation , and the cumulative incidence of ARC were not significantly affected by the probiotic regime at 6 years of age . Conclusions Maternal probiotic ingestion alone may be sufficient for long term reduction in the cumulative incidence of AD , but not other allergy related diseases . Trial registration Clinical Trials.gov identifier : Background : The gut microbiome in infancy influences immune system maturation , and may have an important impact on allergic disease risk . Objective : We sought to determine how prenatal and early life factors impact the gut microbiome in a relatively large , ethnically diverse study population of infants at age 3 to 6 months , who were enrolled in Vitamin D Antenatal Asthma Reduction Trial , a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring . Methods : We performed 16S rRNA gene sequencing on 333 infants ' stool sample s. Microbial diversity was computed using the Shannon index . Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups ; the first dominated by Firmicutes ( Lachnospiraceae/Clostridiales ) , the second by Proteobacteria ( Klebsiella/Enterobacter ) , the third by Bacteriodetes , and the fourth by Veillonella . Scores for coabundance groups were used as outcomes in regression models , with prenatal/birth and demographic characteristics as independent predictors . Multivariate analysis , using all microbial community members , was also conducted . Results : White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores . C‐section birth was associated with higher diversity , but decreased Bacteroidetes coabundance scores . Firmicutes scores were higher for infants born by C‐section . Breast‐fed infants had lower proportions of Clostridiales . Cord blood vitamin D was linked to increased Lachnobacterium , but decreased Lactococcus . Conclusions : The findings presented here suggest that race , mode of delivery , breast‐feeding , and cord blood vitamin D levels are associated with infant gut microbiome composition , with possible long‐term implication s for immune system modulation and asthma/allergic disease incidence Background The 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 . Prebiotics – non-digestible oligosaccharides that stimulate growth of probiotic bacteria – 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 prebiotics in the prevention of allergy . Methods The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy . We performed a systematic review of r and omized controlled trials of prebiotics , and review ed the evidence about patient values and preferences , and re source requirements ( up to January 2015 , with an up date on July 29 , 2015 ) . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . Results Based on GRADE evidence to decision frameworks , the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants . Both recommendations are conditional and based on very low certainty of the evidence . We found no experimental or observational study of prebiotic supplementation  in pregnant women or in breastfeeding mothers . Thus , the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding , at this time . Conclusions WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy , term infants BACKGROUND The intestinal microflora is a likely source for the induction of immune deviation  in infancy . OBJECTIVE The purpose of this study was to prospect ively relate the intestinal microflora to allergy development in 2 countries differing with respect to the prevalence of atopic diseases . METHODS Newborn infants were followed prospect ively through the first 2 years of life in Estonia ( n = 24 ) and Sweden ( n = 20 ) . By that age , 9 Estonian and 9 Swedish infants had developed atopic dermatitis and /or positive skin prick test results .  Stool sample s were obtained at 5 to 6 days and at 1 , 3 , 6 , and 12 months , and 13 groups of aerobic and anaerobic microorganisms were cultivated through use of st and ard methods . RESULTS In comparison with healthy infants , babies who developed allergy were less often colonized with enterococci during the first month of life ( 72 % vs 96 % ; P < .05 ) and with bifidobacteria during the first year of life ( 17 % to 39 % vs 42 % to 69 % ; P < .05 ) . Furthermore , allergic infants had higher counts of clostridia at 3 months ( median value , 10.3 vs 7.2 log(10 ) ; P < .05 ) . The prevalence of colonization with Staphylococcus aureus was also higher at 6 months ( 61 % vs 23 % ; P < .05 ) , whereas the counts of Bacteroides were lower at 12 months ( 9.9 vs 10.6 log(10 ) ; P < .05 ) . CONCLUSION Differences in the composition of the gut flora between infants who will and infants who will not develop allergy are demonstrable before the development of any clinical manifestations of atopy . Because the observations were made in 2 countries with different st and ards of living , we believe that our findings could indicate a role for the intestinal microflora in the development of and protection from allergy Objectives The aim of this study was to assess the efficacy of oral supplementation of viable and heat-inactivated probiotic bacteria in the management of atopic disease and to observe their effects on the composition of the gut microbiota . Methods The study population included 35 infants with atopic eczema and allergy to cow 's milk . At a mean age of 5.5 months , they were assigned in a r and omized double-blind manner to receive either extensively hydrolyzed whey formula ( placebo group ) or the same formula supplemented with viable ( viable LGG group ) or heat-inactivated Lactobacillus GG ( heat-inactivated LGG group ) , respectively . The changes in symptoms were assessed by the SCORAD method and the presence of some predominant bacterial genera in the feces detected with 16S rRNA-specific probes . Results The treatment with heat-inactivated LGG was associated with adverse gastrointestinal symptoms and diarrhea . Consequently , the recruitment of patients was stopped after the pilot phase . Within the study population , atopic eczema and subjective symptoms were significantly alleviated in all the groups ; the SCORAD scores ( interquartile range ) decreased from 13 ( range , 4–29 ) to 8 ( range , 0–29 ) units in the placebo group , from 19 ( range , 4–47 ) to 5 ( range , 0–18 ) units in the viable LGG group , and from 15 ( range , 0–29 ) to 7 ( range , 0–26 ) units in the heat-inactivated LGG group . The decrease in the SCORAD scores within the viable LGG group tended to be greater than within the placebo group . The treatments did not appear to affect the bacterial numbers within the genera enumerated . Conclusions Supplementation of infant formulas with viable but not heat-inactivated LGG is a potential approach for the management of atopic eczema and cow 's milk allergy
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
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 .