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
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
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 .