Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics Prebiotic‐supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high‐risk infants: a randomized controlled trial A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. Oligofructose-supplemented infant cereal: 2 randomized, blinded, community-based trials in Peruvian infants. Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study Effect of a Milk Formula With Prebiotics on the Intestinal Microbiota of Infants After an Antibiotic Treatment Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? A novel galactooligosaccharide mixture increases the bifidobacterial population numbers in a continuous in vitro fermentation system and in the proximal colonic contents of pigs in vivo. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Non-digestible oligosaccharides reduce immunoglobulin free light-chain concentrations in infants at risk for allergy. Bifidogenic Effects of Solid Weaning Foods With Added Prebiotic Oligosaccharides: A Randomised Controlled Clinical Trial Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study. Prebiotic Oligosaccharides in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition [Randomised placebo controlled double blind study on the effect of prebiotic oligosaccharides on intestinal flora in healthy infants]. Colon Microflora in Infants Fed Formula with Galacto- and Fructo-Oligosaccharides: More Like Breast-Fed Infants Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants.
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 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 : 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 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 Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months , but evidence is mixed . Adding specific oligosaccharides may improve outcomes Background : Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora . Aims : To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis ( AD ) during the first six months of life in formula fed infants at high risk of atopy . Methods : Prospect i ve , double-blind , r and omised , placebo controlled trial ; 259 infants at risk for atopy were enrolled . A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study . If bottle feeding was started , the infant was r and omly assigned to one of two hydrolysed protein formula groups ( 0.8 g/100 ml prebiotics or maltodextrine as placebo ) . All infants were examined for clinical evidence of atopic dermatitis . In a subgroup of 98 infants , faecal flora was analysed . Results : Ten infants ( 9.8 % ; 95 CI 5.4–17.1 % ) in the intervention group and 24 infants ( 23.1 % ; 95 CI 16.0–32.1 % ) in the control group developed AD . The severity of the dermatitis was not affected by diet . Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts . Conclusion : Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants . Although the mechanism of this effect requires further investigation , it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy BACKGROUND Most infants developing atopic dermatitis have a low risk for atopy . Primary prevention of atopic dermatitis is difficult . OBJECTIVE To assess the effect of supplementation of an infant and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life . METHODS Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks , either having started with formula feeding or being on full breast-feeding ( breast-feeding group ) . Formula-fed infants were r and omized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides ( prebiotic formula group ) or regular formula without oligosaccharides ( control formula group ) . RESULTS A total of 414 infants were r and omized to the prebiotic group and 416 infants to the control group . A total of 300 infants were followed in the breast-feeding group . Up to the first birthday , atopic dermatitis occurred in significantly fewer infants from the prebiotic group ( 5.7 % ) than from the control group ( 9.7 % ; P = .04 ) . The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group ( 7.3 % ) . In a Cox regression model , the rate of atopic dermatitis was significantly lower by 44 % in the prebiotic group versus the control group ( P = .04 ) . The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants . CONCLUSION Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants BACKGROUND Prebiotics are nondigestible food ingredients that stimulate the growth of Bifidobacterium and other bacteria in the gastrointestinal tract . Improved gastrointestinal and other health effects have been attributed to them . OBJECTIVE The objective of this study was to evaluate the effects of dietary supplementation with the prebiotic oligofructose with and without zinc on the prevalence of diarrhea in a community with a high burden of gastrointestinal and other infections . DESIGN Two consecutive r and omized , blinded , controlled clinical trials were performed in a shantytown community near Lima , Peru . The first trial compared an infant cereal supplemented with oligofructose ( 0.55 g/15 g cereal ) with nonsupplemented cereal . During the second trial , zinc ( 1 mg/15 g cereal ) was added to both oligofructose-supplemented and control cereals . RESULTS We enrolled 282 infants in the first trial and 349 in the second . In the first trial , mean ( + /- SD ) days of diarrhea were 10.3 + /- 9.6 in the nonsupplemented cereal group and 9.8 + /- 11.0 in the prebiotic-supplemented cereal group ( P = 0.66 ) . In the second trial , mean days of diarrhea were 10.3 + /- 8.9 in the group consuming cereal fortified only with zinc and 9.5 + /- 8.9 in the group consuming cereal containing both zinc and prebiotics ( P = 0.35 ) . Postimmunization titers of antibody to Haemophilus influenzae type B were similar in all groups , as were gains in height , visits to clinic , hospitalizations , and use of antibiotics . CONCLUSIONS Cereal supplemented with prebiotics was not associated with any change in diarrhea prevalence , use of health care re sources , or response to H. influenzae type B immunization .  Infants and young children who continue to breast-feed may not benefit from prebiotic supplementation Background Prevention of serious infections in preterm infants is a challenge , since prematurity and low birth weight often requires many interventions and high utility of devices . Furthermore , the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system . In combination with delayed intestinal bacterial colonisation compared with term infants , this may increase the risk for serious infections . Acidic and neutral oligosaccharides play an important role in the development of the immune system , intestinal bacterial colonisation and functional integrity of the gut . This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity ( primary outcome ) , immune response to immunizations , feeding tolerance and short-term and long-term outcome in preterm infants . In addition , an attempt is made to eluci date the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut . Methods / Design In a double-blind placebo controlled r and omised trial , 120 preterm infants ( gestational age < 32 weeks and /or birth weight < 1500 gram ) are r and omly allocated to receive enteral acidic and neutral oligosaccharides supplementation ( 20%/80 % ) or placebo supplementation ( maltodextrin ) between day 3 and 30 of life . Primary outcome is infectious morbidity ( defined as the incidence of serious infections ) . The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations , plasma cytokine concentrations , faecal Calprotectin and IL-8 . The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance , intestinal permeability , intestinal viscosity , and determining intestinal microflora . Furthermore , short-term and long-term outcome are evaluated . Discussion Especially preterm infants , who are at increased risk for serious infections , may benefit from supplementation of prebiotics . Most studies with prebiotics only focus on the colonisation of the intestinal microflora . However , the pathways how prebiotics may influence the immune system are not yet fully understood . Study ing the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants . The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system . Increased insight in the effects of prebiotics on the developing immune system may help to decrease the ( infectious ) morbidity and mortality in preterm infants . Trial registration Current Controlled Trials IS RCT N16211826 Antibiotics exert deleterious effects on the intestinal microbiota , favoring the emergence of opportunistic bacteria and diarrhea . Prebiotics are nondigestible food components that stimulate the growth of bifidobacteria . Our aim was to evaluate the effects on the intestinal microbiota of a prebiotic-supplemented milk formula after an antibiotic treatment . A r and omized , double-blind , controlled clinical trial was carried out in 140 infants 1–2 y of age distributed into two groups after a 1-wk amoxicillin treatment ( 50 mg/kg/d ) for acute bronchitis . The children received for 3 wk > 500 mL/d of a formula with prebiotics ( 4.5 g/L ) or a control without prebiotics . Fecal sample s were obtained on d –7 ( at the beginning of the antibiotic treatment ) , on d 0 ( end of the treatment and before formula administration ) , and on d 7 and 21 ( during formula administration ) . Counts of Bifidobacterium , Lactobacillus-Enterococcus , Clostridium lituseburiense cluster , Clostridium histolyticum cluster , Escherichia coli , and Bacteroides-Prevotella were evaluated by fluorescent in situ hybridization ( FISH ) and flow cytometry . Tolerance and gastrointestinal symptoms were recorded daily . Amoxicillin decreased total fecal bacteria and increased E. coli . The prebiotic significantly increased bifidobacteria from 8.17 ± 1.46 on d 0 to 8.54 ± 1.20 on d 7 compared with the control 8.22 ± 1.24 on d 0 versus 7.95 ± 1.54 on d 7 . The Lactobacillus population showed a similar tendency while the other bacteria were unaffected . No gastrointestinal symptoms were detected during the prebiotic administration . Prebiotics in a milk formula increase fecal bifidobacteria early after amoxicillin treatment without inducing gastrointestinal symptoms 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 Prebiotics are nondigestible food ingredients that encourage proliferation of selected groups of the colonic microflora , thereby altering the composition toward a more beneficial community . In the present study , the prebiotic potential of a novel galactooligosaccharide ( GOS ) mixture , produced by the activity of galactosyltransferases from Bifidobacterium bifidum 41171 on lactose , was assessed in vitro and in a parallel continuous r and omized pig trial .  In situ fluorescent hybridization with 16S rRNA-targeted probes was used to investigate changes in total bacteria , bifidobacteria , lactobacilli , bacteroides , and Clostridium histolyticum group in response to supplementing the novel GOS mixture . In a 3-stage continuous culture system , the bifidobacterial numbers for the first 2 vessels , which represented the proximal and traverse colon , increased ( P < 0.05 ) after the addition of the oligosaccharide mixture . In addition , the oligosaccharide mixture strongly inhibited the attachment of enterohepatic Escherichia coli ( P < 0.01 ) and Salmonella enterica serotype Typhimurium ( P < 0.01 ) to HT29 cells . Addition of the novel mixture at 4 % ( wt : wt ) to a commercial diet increased the density of bifidobacteria ( P < 0.001 ) and the acetate concentration ( P < 0.001 ) , and decreased the pH ( P < 0.001 ) compared with the control diet and the control diet supplemented with inulin , suggesting a great prebiotic potential for the novel oligosaccharide mixture Development of oral tolerance and its stimulation by probiotics are still incomprehensible . Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA , which participates in antigen elimination . In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo  we studied intestinal IgA and inflammation in the development of eczema , food allergy , asthma , and rhinitis ( allergic diseases ) . We performed a nested unmatched case-control study of 237 infants participating in a r and omized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth . We measured faecal IgA , alpha1-antitrypsin ( alpha1-AT ) , tumour necrosis factor-alpha ( TNF-alpha ) , and calprotectin  at the age of 3 and 6 months . By age 2 yr , 124 infants had developed allergic disease or IgE-sensitization  ( cases ) and 113 had not ( controls ) . In infants with high faecal IgA concentration at the age of 6 months , the risk of having any allergic disease before the age of 2 yr tended to reduce [ odds ratio ( OR : 0.52 ) ] and the risk for any IgE-associated ( atopic ) disease reduced significantly ( OR : 0.49 ) . High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr ( OR : 0.49 ) . All faecal inflammation markers ( alpha1-AT , TNF-alpha , and calprotectin ) correlated positively with faecal IgA ( p < 0.001 ) . Probiotics tended to augment faecal IgA ( p = 0.085 ) and significantly increased faecal alpha1-AT ( p = 0.001 ) . High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases Prebiotic oligosaccharides influence the intestinal microbiota and can positively modulate the infant 's immune system . It was demonstrated that a special prebiotic mixture ( Immunofortis ( ® ) ) of short-chain galacto-oligosaccharides ( scGOS ) and long-chain fructo-oligosaccharides ( lcFOS ) can reduce the cumulative incidence of atopic dermatitis ( AD ) in infants at risk for allergy as determined using the AD symptom score ( SCORAD ) . Additionally , it was shown very recently that immunoglobulin free light-chain ( Ig-fLC ) might be involved in the pathophysiology of allergic disease . Increased Ig-fLC concentrations were found in patients suffering from AD , cow 's milk allergy , allergic rhinitis , or asthma . In this study , the effect of supplementation of scGOS/lcFOS on the Ig-fLC plasma concentrations in infants at risk for allergy was assessed . The plasma kappa and lambda Ig-fLC concentrations were measured in a double-blind , placebo-controlled , r and omized trial , in which infants at risk for developing allergic disease received a  hypoallergenic whey formula containing 8 g/l of the scGOS/lcFOS mixture ( n = 34 ) or maltodextrin as a placebo ( n=40 ) for 6 months . After intervention , plasma sample s were collected , and total plasma concentrations of lambda and kappa Ig-fLC were analyzed using ELISA . Total kappa and lambda Ig-fLC plasma concentrations were higher in infants suffering from AD when compared to infants without any sign of AD . In infants receiving the prebiotic mixture  , the Ig-fLC levels were significantly lower compared to the placebo-fed infants ( p<0.001 ) . Interestingly , lambda Ig-fLC concentrations were positively correlated with total IgE ( p<0.05 ) . These data demonstrate for the first time that the specific scGOS/lcFOS mixture lowered kappa and lambda Ig-fLC plasma concentrations in infants at high risk for allergies when compared to infants receiving placebo formula . Because Ig-fLC concentrations were increased in infants suffering from AD , this may have contributed , at least in part , to the reduced incidence in AD as described previously . This suggests a possible role for Ig-fLC in the pathophysiology of AD in infants at risk for allergy development Objectives : Breast-fed infants have relatively high proportions of faecal bifidobacteria . This bifidogenic microbiota is at least partly explained by the high levels of prebiotic oligosaccharides in human milk . The present study aim ed at testing the effect of solid foods with added prebiotic galacto- and fructo-oligosaccharides ( GOS/FOS ) on the composition of the intestinal microbiota of fully formula-fed infants during the weaning period . Methods : The study was a double-blind , r and omised trial with an intervention period of 6 weeks . Infants aged 4 to 6 months who were about to start consuming solid foods were r and omised to receive either weaning products with a mixture of GOS/FOS or control weaning products with maltodextrin . After an adjustment period , the presented daily dose of GOS/FOS was 4.5 g. Total numbers of bacteria and bifidobacteria in faecal sample s were analysed with fluorescent in situ hybridization . Results : Thirty-five infants were included in the study , and 20 infants were included in a per- protocol analysis . In the GOS/FOS group , the faecal percentage of bifidobacteria significantly increased from 43 % to 57 % ( P = 0.031 ) from week 0 to week 6 , but did not significantly change in the control group ( 36 % and 32 % , respectively ; P = 0.387 ) . The change in the percentage of bifidobacteria between week 0 and week 6 in the GOS/FOS was significantly different from this change in the control group ( P = 0.026 ) . Conclusions : We conclude that addition of GOS/FOS to solid foods induces an increase in the faecal proportion of bifidobacteria in the intestinal microbiota of fully formula-fed infants with an established , mixed-type microbiota in the weaning period A mixture of neutral short-chain galactooligosaccharides ( scGOS ) and long-chain fructooligosaccharides ( lcFOS ) has been shown to reduce the incidence of atopic dermatitis ( AD ) and infectious episodes during the first 6 mo of life . This dual protection occurred through the intervention period . The present study evaluated if these protective effects were lasting beyond the intervention period . In a prospect i ve , r and omized , double-blind , placebo-controlled design , healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented ( 8 g/L scGOS/lcFOS ) or placebo-supplemented ( 8 g/L maltodextrin ) hypoallergenic formula during the first 6 mo of life . Following this intervention period , blind follow-up continued until 2 y of life . Primary endpoints were cumulative incidence of allergic manifestations . Secondary endpoints were number of infectious episodes and growth .  Of 152 participants , 134 infants ( 68 in placebo , 66 in intervention group ) completed the follow-up . During this period , infants in the scGOS/lcFOS group had significantly lower incidence of allergic manifestations . Cumulative incidences for AD , recurrent wheezing , and allergic urticaria were higher in the placebo group , ( 27.9 , 20.6 , and 10.3 % , respectively ) than in the intervention group ( 13.6 , 7.6 , and 1.5 % ) ( P < 0.05 ) . Infants in the scGOS/lcFOS group had fewer episodes of physician-diagnosed overall and upper respiratory tract infections ( P < 0.01 ) , fever episodes ( P < 0.00001 ) , and fewer antibiotic prescriptions ( P < 0.05 ) . Growth was normal and similar in both groups . Early dietary intervention with oligosaccharide prebiotics has a protective effect against both allergic manifestations and infections . The observed dual protection lasting beyond the intervention period suggests that an immune modulating effect through the intestinal flora modification may be the principal mechanism of action BACKGROUND & AIM The addition of prebiotics to infant formula modifies the composition of intestinal microflora . Aim of the study was to test the hypothesis that prebiotics reduce the incidence of intestinal and respiratory infections in healthy infants . METHODS A prospect i ve , r and omized , placebo-controlled , open trial was performed . Healthy infants were enrolled and r and omized to a formula additioned with a mixture of galacto- and fructo-oligosaccharides or to a control formula . The incidence of intestinal and respiratory tract infections and the anthropometric measures were monitored for 12 months . RESULTS Three hundred and forty two infants ( mean age 53.7+/-32.1 days ) were enrolled . The incidence of gastroenteritis was lower in the supplemented group than in the controls ( 0.12+/-0.04 vs. 0.29+/-0.05 episodes/child/12 months ; p=0.015 ) . The number of children with more than 3 episodes tended to be lower in prebiotic group ( 17/60 vs. 29/65 ; p=0.06 ) . The number of children with multiple antibiotic courses/year was lower in children receiving prebiotics ( 24/60 vs. 43/65 ; p=0.004 ) . A transient increase in body weight was observed in children on prebiotics compared to controls during the first 6 months of follow-up . CONCLUSIONS Prebiotic administration reduce intestinal and , possibly , respiratory infections in healthy infants during the first year of age This article by the ESPGHAN Committee on Nutrition summarizes available information on the effects of adding prebiotic oligosaccharides to infant and follow-on formulae . Currently there are only limited studies evaluating prebiotic substances in dietetic products for infants . Although administration of prebiotic oligosaccharides has the potential to increase the total number of bifidobacteria in feces and may also soften stools , there is no published evidence of clinical benefits of adding prebiotic oligosaccharides to dietetic products for infants . Data on oligosaccharide mixtures in infant formulae do not demonstrate adverse effects , but further evaluation is recommended . Combinations and dosages in addition to those so far studied need to be fully evaluated with respect to both safety and efficacy before their use in commercial infant food products . Well- design ed and carefully conducted r and omized controlled trials with relevant inclusion /exclusion criteria , adequate sample sizes and vali date d clinical outcome measures are needed both in preterm and term infants . Future trials should define optimal quantity and types of oligosaccharides with prebiotic function , optimal dosages and duration of intake , short and long term benefits and safety . At the present time , therefore , the Committee takes the view that no general recommendation on the use of oligosaccharide supplementation in infancy as a prophylactic or therapeutic measure can be made AIM Effects of supplementing prebiotic oligosaccharides to formula for healthy infants were studied in this placebo controlled , r and omised , double blind study . METHODS Ninety-seven infants were included into the study ; among them 42 breast-fed infants , 14 infants fed formula supplemented with 0.4 g/100ml oligosaccharides ( 9 to 1 mixture of galacto- and fructooligosaccharides ) and 13 infants fed control formula  were followed-up throughout the 12-week-long study period . The groups receiving formula were compared with statistical methods , whereas data of breast-fed infants served as reference values . RESULTS Infants fed the two formulae did not differ in nutrient intakes , growth , occurrence rate of feeding difficulties and atopic manifestations , or in calcium excretion . The intestinal flora did not differ between the two formula fed groups at the beginning of the study . In contrast , numbers of Bifidobacteriae were significantly higher in infants receiving the formula supplemented with prebiotic oligosaccharides both at the 14th day ( 9 x 1011 versus 5 x 1010 , colony forming units/g faeces , median , p < 0.05 ) and 28th day ( 9 x 1012 versus 5 x 1010 , p < 0.05 ) of the study . CONCLUSION In this study , supplementation of infant formula with prebiotic oligosaccharides result ed in ameliorating the difference in intestinal flora between formula fed and breast-fed healthy infants Objectives : The intestinal flora of breast-fed infants is generally dominated by Bifidobacteria . We aim ed to investigate whether an infant formula supplemented with galacto-oligosaccharides and fructo-oligosaccharides ( GOS/FOS ) is able to establish a bifido-dominant microflora , not only in numbers but also with respect to the metabolic activity in the colon . Methods : Two groups of infants fed infant formula with 0.8 g/100 ml GOS/FOS in a ratio of 9:1 ( OSF group ) , or control formula ( SF group ) were evaluated in a r and omised , double blind , placebo controlled intervention study . A breast-fed group was studied in parallel . At study onset and after 4 and 6 weeks , faecal sample s were examined for the number of bifidobacteria , pH , short chain fatty acids and lactate . Results : After 6 weeks , the mean proportion of bifidobacteria was significantly higher in the OSF group ( 59.6 % versus 49.5 % in the SF group ; P < 0.05 ) . Compared with controls , infants in the OSF group had a lower stool mean pH and an increased proportion of acetate and a decreased proportion of propionate . The mean pH in the OSF and SF groups were 5.7 and 6.3 , respectively ( P < 0.001 ) . Conclusions : The addition of the prebiotic GOS/FOS mixture to an infant formula has a stimulating effect on the growth of bifidobacteria and on the metabolic activity of the total intestinal flora . The changes in short chain fatty acids , lactate and pH in the prebiotic group represent a fermentation profile that is closer to that observed in breast-fed infants compared to infants fed control formula Necrotizing enterocolitis ( NEC ) continues to be a major cause of morbidity and mortality in premature infants . Although the pathogenesis of NEC remains unclear , abnormal bacterial colonization has been postulated as playing a central role . Various factors impact bacterial colonization following delivery . Compared to term infants , the bacterial colonization pattern in prematurely born infants is markedly different , with a greater predilection for colonization with pathogenic bacteria . Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment , favoring the growth of commensal bacteria . Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC . These preliminary studies support the need for a large , r and omized , controlled trial to further investigate the role of probiotics in the prevention of NEC AIM The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various components of breast milk , including prebiotic substances . This prospect i ve double-blind study compared the numbers of bifidobacteria in the stool flora of bottle-fed preterm infants r and omized to receive for 14 days either a formula with prebiotic fructo-oligosaccharides at a concentration of 0.4 g/dL or the same formula with maltodextrin as a placebo . METHODS Within 0 - 14 days after birth , 56 healthy bottle-fed infants were enrolled to receive either the prebiotic or placebo . Faecal sample s were taken at inclusion day and at study day 7 . The number of bifidobacteria in the stools , stool characteristics and somatic growth were recorded during the study . RESULTS In the group fed fructo-oligosaccharides , both the numbers of bifidobacteria in the stools and the proportion of infants colonized with them were significantly higher as compared to the placebo group ( p=0.032 and p=0.030 respectively ) . There was also a higher number of bacteroids in the fructo-oligosaccharide group as compared to the placebo ( p=0.029 ) . At the same time , reduction was noted in the numbers of Escherichia coli and enterococci . ( p=0.029 , and p=0.025 , respectively ) . Supplementation had also significant influence on stool frequency per day ( p=0.0080 ) . CONCLUSION An infant formula containing a small quantity of prebiotic oligosaccharides is well accepted and leads to rapid growth of bifidobacteria in the gut of bottle-fed preterm infants while decreasing the numbers of pathogenic microorganisms BACKGROUND Alterations in intestinal microflora have been linked to the development of allergic disease . Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains . OBJECTIVES We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life . METHODS Fecal sample s were collected 1 wk after birth from 98 infants at high risk of allergic disease , who were followed prospect ively to age 12 months .  Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism ( T-RFLP ) using restriction enzymes Sau96I and AluI , with a greater number of peaks representing greater diversity of bacterial communities . RESULTS Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema ( AluI mean number of peaks 13.1 vs. 15.5 , p = 0.003 , 95 % CI for difference in means -3.9 , -0.8 ; Sau96I 14.7 vs. 17.2 , p = 0.03 , 95 % CI -4.9 , -0.3 ) . No differences were observed for atopic compared to non-atopic infants , or infants with two allergic parents compared to those with one or no allergic parent . CONCLUSIONS A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease . Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants
Differences were potentially attributable to differences in infant risk , prebiotic formulation or measurement of eczema .
There is insufficient evidence to determine the role of prebiotic supplementation of infant formula for prevention of allergic disease and food hypersensitivity .
Further trials are needed to determine whether this finding persists over a longer period of time , applies to other manifestations of allergic disease , is associated with reductions in allergen sensitisation , and is reproducible
BACKGROUND The composition of the intestinal microflora may be different in individuals with atopic eczema from those without this condition , and such differences may precede the development of eczema .
Prebiotics are nondigestible food components that benefit the host by selectively stimulating the growth or activity of non-pathogenic bacteria in the colon .
Prebiotics ( commonly oligosaccharides ) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens .
OBJECTIVES To determine the effect of prebiotics given to infants for the prevention of allergic disease or food hypersensitivity .