title: Effect of a Probiotic Infant Formula on Infections in Child Care Centers: Comparison of Two Probiotic Agents Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial. Quantitative Real-Time PCR Assays To Identify and Quantify Fecal Bifidobacterium Species in Infants Receiving a Prebiotic Infant Formula Fecal secretory immunoglobulin A is increased in healthy infants who receive a formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled 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. Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety. Effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the intestinal microflora during the first 4 months of life. Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial Dosage-Related Bifidogenic Effects of Galacto- and Fructooligosaccharides in Formula-Fed Term Infants Effect of a Milk Formula With Prebiotics on the Intestinal Microbiota of Infants After an Antibiotic Treatment Acidic Oligosaccharides from Pectin Hydrolysate as New Component for Infant Formulae: Effect on Intestinal Flora, Stool Characteristics, and pH Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli. Reduction of rotavirus infection in children receiving bifidobacteria-supplemented formula. Colon Microflora in Infants Fed Formula with Galacto- and Fructo-Oligosaccharides: More Like Breast-Fed Infants The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Acidified Milk Formula Supplemented With Bifidobacterium lactis: Impact on Infant Diarrhea in Residential Care Settings Safety and Tolerance of a Probiotic Formula in Early Infancy Comparing Two Probiotic Agents: A Pilot Study Effect of a fermented infant formula containing viable bifidobacteria on the fecal flora composition and pH of healthy full-term infants. [Randomised placebo controlled double blind study on the effect of prebiotic oligosaccharides on intestinal flora in healthy infants]. A Randomized Formula Controlled Trial of Bifidobacterium lactis and Streptococcus thermophilus for Prevention of Antibiotic-Associated Diarrhea in Infants Growth during the first 6 months of life in infants using formula enriched with Lactobacillus rhamnosus GG: double-blind, randomized trial. Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics for Primary Prevention: No Clinical Effects of Lactobacillus GG Supplementation Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics. Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants. Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants. The effect of a prebiotic supplemented formula on growth and stool microbiology of term infants. Prebiotic Oligosaccharides in Dietetic Products for Infants: A Commentary by the ESPGHAN Committee on Nutrition Effects of a new mixture of prebiotics on faecal flora and stools in term infants Term Infants Fed Formula Supplemented With Selected Blends of Prebiotics Grow Normally and Have Soft Stools Similar to Those Reported for Breast-fed Infants Effect of bifidobacterium Bb12 with or without Streptococcus thermophilus supplemented formula on nutritional status. Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Effects on Faecal Microbiota of Dietary and Acidic Oligosaccharides in Children During Partial Formula Feeding Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial Urinary D-Lactate Excretion in Infants Receiving Lactobacillus johnsonii with Formula Effect of prebiotic galacto-oligosaccharide, long-chain fructo-oligosaccharide infant formula on serum cholesterol and triacylglycerol levels. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus Growth and Tolerance of Healthy Term Infants Receiving Hydrolyzed Infant Formulas Supplemented With Lactobacillus rhamnosus GG: Randomized, Double-Blind, Controlled Trial Safety and tolerance of the human milk probiotic strain Lactobacillus salivarius CECT5713 in 6-month-old children.
abstract: Objective . To investigate the effect of 2 different species of probiotics in preventing infections in infants attending child care centers . Methods . A double-blind , placebo-controlled , r and omized trial was conducted from December 1 , 2000 , to September 30 , 2002 , at 14 child care centers in the Beer-Sheva area of Israel in healthy term infants 4 to 10 months old . Infants were assigned r and omly to formula supplemented with Bifidobacterium lactis ( BB-12 ) , Lactobacillus reuteri ( American Type Culture Collection 55730 ) , or no probiotics . Duration of feeding , including follow-up , for each participant was 12 weeks . All infants were fed only the assigned formula and were not breastfed due to parental decision before recruitment to the study . Probiotic or prebiotic food products or supplements were not allowed . Main outcome measures were number of days and number of episodes with fever ( > 38 ° C ) and number of days and number of episodes with diarrhea or respiratory illness . Results . Participants ( n = 201 ) were similar regarding gestational age , birth weight , gender , and previous breastfeeding . The controls ( n = 60 ) , compared with those fed B lactis ( n = 73 ) or L reuteri ( n = 68 ) , had significantly more febrile episodes ( mean [ 95 % confidence interval ] : 0.41 [ 0.28–0.54 ] vs 0.27 [ 0.17–0.37 ] vs 0.11 [ 0.04–0.18 ] , respectively ) . The controls also had more diarrhea episodes ( 0.31 [ 0.22–0.40 ] vs 0.13 [ 0.05–0.21 ] vs 0.02 [ 0.01–0.05 ] , respectively ) and episodes of longer duration ( 0.59 [ 0.34–0.84 ] vs 0.37 [ 0.08–0.66 ] vs 0.15 [ 0.12–0.18 ] days , respectively ) . The L reuteri group , compared with BB-12 or controls , had a significant decrease of number of days with fever , clinic visits , child care absences , and antibiotic prescriptions . Rate and duration of respiratory illnesses did not differ significantly between groups . Conclusions . Child care infants fed a formula supplemented with L reuteri or B lactis had fewer and shorter episodes of diarrhea , with no effect on respiratory illnesses . These effects were more prominent with L reuteri , which was also the only supplement to improve additional morbidity parameters The addition of probiotics to infant formula has been shown to be an efficient way to increase the number of beneficial bacteria in the intestine in order to promote a gut flora resembling that of breast-fed infants . The objective of the present study was to evaluate the safety and tolerance of a combination of two probiotic strains in early infancy . A group of 126 newborns were r and omised to receive a prebiotic-containing starter formula supplemented with Lactobacillus paracasei ssp . paracasei and Bifidobacterium animalis ssp . lactis or the same formula without probiotics for the first 3 months of life . A total of eighty infants continued the study until they were aged 6 months .  Growth measurements were taken monthly at healthy baby clinics . Diaries were used to monitor behaviour , infections , use of antibiotics , as well as stool characteristics . Normal growth occurred in all infants and no statistically significant differences were detected between the probiotics group and the control group for gain in weight , length and head circumference . Infants in the probiotics group produced softer and more frequent stools during the first 3 months of life . No differences were found in crying and sleeping hours , number of parent-diagnosed infections , antibiotic use , visits to the general practitioner and number of adverse events . The use of a prebiotic-containing starter formula supplemented with L. paracasei ssp . paracasei and B. animalis ssp . lactis in early infancy is safe , well tolerated and has no adverse effects on growth and infant behaviour ABSTRACT A healthy intestinal microbiota is considered to be important for priming of the infants ' mucosal and systemic immunity . Breast-fed infants typically have an intestinal microbiota dominated by different Bifidobacterium species . It has been described that allergic infants have different levels of specific Bifidobacterium species than healthy infants . For the accurate quantification of Bifidobacterium adolescentis , Bifidobacterium angulatum , Bifidobacterium bifidum , Bifidobacterium breve , Bifidobacterium catenulatum , Bifidobacterium dentium , Bifidobacterium infantis , and Bifidobacterium longum in fecal sample s , duplex 5′ nuclease assays were developed . The assays , targeting rRNA gene intergenic spacer regions , were vali date d and compared with conventional PCR and fluorescent in situ hybridization methods . The 5′ nuclease assays were subsequently used to determine the relative amounts of different Bifidobacterium species in fecal sample s from infants receiving a st and ard formula or a st and ard formula supplemented with galacto- and fructo-oligosaccharides ( OSF ) . A breast-fed group was studied in parallel as a reference . The results showed a significant increase in the total amount of fecal bifidobacteria ( 54.8 % ± 9.8 % to 73.4 % ± 4.0 % ) in infants receiving the prebiotic formula ( OSF ) , with a diversity of Bifidobacterium species similar to breast-fed infants . The intestinal microbiota of infants who received a st and ard formula seems to resemble a more adult-like distribution of bifidobacteria and contains relatively more B. catenulatum and B. adolescentis ( 2.71 % ± 1.92 % and 8.11 % ± 4.12 % , respectively , versus 0.15 % ± 0.11 % and 1.38 % ± 0.98 % for the OSF group ) . In conclusion , the specific prebiotic infant formula used induces a fecal microbiota that closely resembles the microbiota of breast-fed infants also at the level of the different Bifidobacterium species In this double-blind , r and omized , placebo-controlled study , we investigated the effect of an infant milk formula with 6 g/L short-chain galacto- and long-chain fructo-oligosaccharides [ ( scGOS/lcFOS ) ratio 9:1 ] on the development of the fecal secretory immunoglobulin A ( sIgA ) response and on the composition of the intestinal microbiota in 215 healthy infants during the first 26 wk of life . The infants received breast milk or were r and omized to receive an infant milk formula with or without scGOS/lcFOS . Stool sample s were collected after 8 and 26 wk of intervention . The concentration of fecal sIgA was determined by ELISA , and the composition of the intestinal microbiota was determined by quantitative fluorescent in situ hybridization . The scGOS/lcFOS group and the control group were compared in the statistical analysis . A breast fed group was included as a reference . In total , 187 infants completed the study . After 26 wk of intervention , in infants that were exclusively formula fed , the concentration of sIgA was higher ( P < 0.001 ) in the scGOS/lcFOS group ( 719 microg/g ) than in the control group ( 263 microg/g ) . In addition , the percentages of bifidobacteria were higher in the scGOS/lcFOS group ( 60.4 % ) than in the control group ( 52.6 % , P = 0.04 ) . The percentages of Clostridium spp . were 0.0 and 3.27 % , respectively ( P = 0.006 ) . In conclusion , an infant milk formula with 6 g/L scGOS/lcFOS results in higher concentrations of fecal sIgA , suggesting a positive effect on mucosal immunity A mixture of neutral short chain galactooligosaccharides and long chain fructo-oligosaccharides ( scGOS/lcFOS ) has been shown to have prebiotic and immunomodulatory effects comparable to human milk oligosaccharides . This can be translated into clinical practice as a potential to prevent infections and allergy . The hypothesis of this study was that this specific prebiotic mixture could have a preventive effect against infections during the first 6 mo of life . In a prospect i ve , r and omized , double-blind , placebo-controlled trial , healthy term infants with a parental history of atopy were fed either prebiotic-supplemented ( 8 g/L scGOS/lcFOS ) or placebo-supplemented ( 8 g/L maltodextrin ) hypoallergenic formula during the first 6 mo of life . The primary outcome measures were infectious episodes , number of infections requiring antibiotics , and incidence of infections . During the study period , infants in the scGOS/lcFOS group had fewer episodes of all types of infections combined ( P = 0.01 ) . They also tended to have fewer upper respiratory tract infection episodes ( P = 0.07 ) and fewer infections requiring antibiotic treatment ( P = 0.10 ) . Similarly , the cumulative incidence of recurring infections was significantly lower in the scGOS/lcFOS group . The cumulative incidence of any recurring infection and recurring respiratory infections was 3.9 and 2.9 % in the scGOS/lcFOS group and 13.5 and 9.6 % in the placebo group , respectively ( P < 0.05 ) . Oligosaccharide prebiotics reduced the number of infectious episodes and the incidence of recurring , particularly respiratory , infections during the first 6 mo of life . Although the exact mechanism of action is under investigation , it is very likely that the immune modulating effect of this prebiotic mixture through intestinal flora modification is the principal mechanism for the observed infection prevention early in life BACKGROUND Probiotics and prebiotics are considered to be beneficial to the gastrointestinal health of infants . OBJECTIVE The objective was to evaluate infant formulas containing probiotics and synbiotics ( combinations of probiotics and prebiotics ) for safety and tolerance . DESIGN In a prospect i ve , controlled , double-blind , r and omized trial , healthy full-term infants were exclusively fed a control formula or study formulas containing Bifidobacterium longum BL999 ( BL999 ) + Lactobacillus rhamnosus LPR ( LPR ) , BL999 + LPR + 4 g/L of 90 % galactooligosaccharide/10 % short-chain fructooligosaccharide ( GOS/SCFOS ) , or BL999 + Lactobacillus paracasei ST11 ( ST11 ) + 4 g/L GOS/SCFOS from < or = 2 to 16 wk of age ( treatment period ) . Safety and tolerance were assessed based on weight gain during the treatment period ( primary outcome ) as well as recumbent length , head circumference , digestive tolerance , and adverse events ( secondary outcomes ) , which were evaluated at 2 , 4 , 8 , 12 , 16 , and 52 wk of age . RESULTS Two hundred eighty-four infants were enrolled . During the treatment period , difference in mean weight gain between control and study formula groups in both the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d , indicating equivalent weight gain . Secondary outcomes did not show significant differences between groups during the treatment period . CONCLUSION Infants fed formulas containing probiotics or synbiotics show a similar rate in weight gain compared with those fed a control formula and tolerate these formulas well 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 Nonpathogenic live bacteria are consumed as food by many children , particularly in the form of yogurt . The tolerance and safety of long-term consumption of specific types and strains of probiotic bacteria are not well documented . OBJECTIVE The goal was to evaluate tolerance to formulas containing 2 levels of probiotic supplementation and effects on growth , general clinical status , and intestinal health in free-living healthy infants . DESIGN This was a prospect i ve , double-blind , r and omized , placebo-controlled study of healthy infants aged 3 - 24 mo . Infants were assigned to receive a st and ard milk-based formula containing 1 x 10(7 ) colony-forming units (CFU)/g each of Bifidobacterium lactis and Streptococcus thermophilus , formula containing 1 x 10(6 ) CFU/g each of B. lactis and S. thermophilus , or unsupplemented formula . Clinical outcomes included formula intake , gastrointestinal tolerance , anthropometric measures , daycare attendance , and history of illness . RESULTS One hundred eighteen infants aged ( + /- SD ) 7.0 + /- 2.9 mo at enrollment consumed formula for 210 + /- 127 d. There were no significant differences in age , sex , formula consumption , or length of study between groups . The supplemented formulas were well accepted and were associated with a lower frequency of reported colic or irritability ( P < 0.001 ) and a lower frequency of antibiotic use ( P < 0.001 ) than was the unsupplemented formula . There were no significant differences between groups in growth , health care attention seeking , daycare absenteeism , or other health variables . CONCLUSION Long-term consumption of formulas supplemented with B. lactis and S. thermophilus was well tolerated and safe and result ed in adequate growth , reduced reporting of colic or irritability , and a lower frequency of antibiotic use Adding prebiotics or probiotics to infant formula to improve the intestinal flora of formula-fed infants is considered to be a major innovation . Several companies have brought relevant formulations onto the market . However , comparative data on the effects of pre- and probiotics on the intestinal microflora of infants are not available . The present study aim ed to compare the effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the composition and metabolic activity of the intestinal microflora . Before birth , infants were r and omised and double blindly allocated to one of three formulas . The prebiotic ( GOS/FOS ) group ( n 19 ) received regular infant formula supplemented with a mixture of galacto-oligosaccharides and fructo-oligosaccharides ( 6 g/l ) . The probiotic ( Bb-12 ) group ( n 19 ) received the same formula supplemented with 6.0x10(10 ) viable cells of B. animalis per litre . The st and ard group ( n 19 ) received non-supplemented regular formula .  A group of sixty-three breast-fed infants was included as a reference group . Faecal sample s were taken at postnatal day 5 and 10 , and week 4 , 8 , 12 and 16 . Compared with the groups fed Bb-12 and st and ard formula , the GOS/FOS formula group showed higher faecal acetate ratio ( 69.7 % ( sem 2.7 ) , 69.9 % ( sem 3.9 ) and 82.2 % ( sem 5.3 ) ; P<0.05 ) and lactate concentration ( 11.3 ( sem 7.9 ) , 3.1 ( sem 2.3 ) and 34.7 ( sem 10.7 ) mmol/kg faeces ) and lower pH ( 6.6 ( sem 0.2 ) , 7.1 ( sem 0.2 ) and 5.6 ( sem 0.2 ) ; P<0.05 ) at 16 weeks . Differences in percentage of bifidobacteria between the GOS/FOS ( 59.2 % ( sem 7.7 ) ) , Bb-12 ( 52.7 % ( sem 8.0 ) ) and the st and ard ( 51.8 % ( sem 6.4 ) ) groups were not statistically significant at 16 weeks . Feeding infants GOS/FOS formula result ed in a similar effect on metabolic activity of the flora as in breast-fed infants . In the Bb-12 group , composition and metabolic activity of the flora were more similar to those of the st and ard group AIMS To study the bacterial diversity in  expressed human milk  with a focus on detecting bacteria with an antimicrobial activity against Staphylococcus aureus , known as a causative agent of maternal breast infections and neonatal infections . METHODS AND RESULTS R and om isolates ( n = 509 ) were collected from breast milk sample s ( n = 40 ) of healthy lactating women , genotypically identified , and tested for antimicrobial activity against Staph . aureus . Commensal staphylococci ( 64 % ) and oral streptococci ( 30 % ) , with Staph . epidermidis , Strep . salivarius , and Strep . mitis as the most frequent isolates , were the predominant bacterial species in breast milk . One-fifth of Staph . epidermidis and half of Strep . salivarius isolates suppressed growth of Staph . aureus . Enterococci ( Ent . faecalis ) , isolated from 7.5 % of sample s , and lactic acid bacteria ( LAB ) ( Lactobacillus rhamnosus , Lact . crispatus , Lactococcus lactis , Leuconoctoc mesenteroides ) , isolated from 12.5 % of sample s , were also effective against Staph . aureus . One L. lactis isolate was shown to produce nisin , a bacteriocin used in food industry to prevent bacterial pathogens and spoilage . CONCLUSIONS Expressed breast milk contains commensal bacteria , which inhibit Staph . aureus . SIGNIFICANCE AND IMPACT OF THE STUDY The strains inhibitory against the pathogen Staph . aureus have potential use as bacteriotherapeutic agents in preventing neonatal and maternal breast infections caused by this bacterium BACKGROUND Severe acute malnutrition affects 13 million children worldwide and causes 1 - 2 million deaths every year . Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting . METHODS We recruited 795 Malawian children ( age range 5 to 168 months [ median 22 , IQR 15 to 32 ] ) from July 12 , 2006 , to March 7 , 2007 , into a double-blind , r and omised , placebo-controlled efficacy trial . For generalisability , all admissions for severe acute malnutrition treatment were eligible for recruitment . After stabilisation with milk feeds , children were r and omly assigned to ready-to-use therapeutic food either with ( n=399 ) or without ( n=396 ) Synbiotic2000 Forte . Average prescribed Synbiotic dose was 10(10 ) colony-forming units or more of lactic acid bacteria per day for the duration of treatment ( median 33 days ) . Primary outcome was nutritional cure ( weight-for-height > 80 % of National Center for Health Statistics median on two consecutive outpatient visits ) . Secondary outcomes included death , weight gain , time to cure , and prevalence of clinical symptoms ( diarrhoea , fever , and respiratory problems ) . Analysis was on an intention-to-treat basis . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N19364765 . FINDINGS Nutritional cure was similar in both Synbiotic and control groups ( 53.9 % [ 215 of 399 ] and 51.3 % [ 203 of 396 ] ; p=0.40 ) . Secondary outcomes were also similar between groups . HIV seropositivity was associated with worse outcomes overall , but did not modify or confound the negative results . Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group ( p=0.06 ) . INTERPRETATION In Malawi , Synbiotic2000 Forte did not improve severe acute malnutrition outcomes . The observation of reduced outpatient mortality might be caused by bias , confounding , or chance , but is biologically plausible , has potential for public health impact , and should be explored in future studies . FUNDING Department for International Development ( DfID ) 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 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 Background Human milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine . In this study , the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low-molecular-weight galactooligosaccharides and high-molecular-weight fructooligosaccharides was analyzed in 90 term infants . Methods Two test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides . In the control formula , maltodextrin was used as placebo . At study day 1 and study day 28 , the fecal species , colony forming units ( cfu ) and pH were measured and stool characteristics , growth , and side effects were recorded . Results At study day 1 , the median number of Bifidobacteria did not differ among the groups ( 0.4 g/dL group , mean [ interquartile range ] 8.5 [ 1.9 ] cfu/g ; 0.8 g/dL group , 7.7 [ 6.1 ] cfu/g ; and the placebo group , 8.8 [ 6.1 ] cfu/g ) ( figures in square brackets are interquartile range ) . At the end of the 28-day feeding period , the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas ( the 0.4 g/dL group , 9.3 [ 4.9 ] cfu/g ; the 0.8 g/dL group , 9.7 [ 0.8 ] cfu/g ) versus the placebo group ( 7.2 [ 4.9 ] cfu/g , P < 0.001 ) . This effect was dose dependent ( 0.4 g/dL versus 0.8 g/dL , P < 0.01 ) . The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas ( versus placebo , P < 0.001 ) , but there was no statistically significant difference between the group fed formula with 0.4 g/dL oligosaccharides and the group fed formula with 0.8 g/dL oligosaccharides . The dosage of supplement significantly influenced the change in fecal pH ( P < 0.05 ) ( placebo , pH 5.5–6.1 ; 0.4 g/dL formula , pH 5.48–5.44 ; 0.8 g/dL formula , pH 5.54–5.19 ) . Slight changes in the stool frequency result ed in a significant difference between the placebo group and the group fed the 0.8 g/dL formula at day 28 ( P < 0.01 ) . Supplementation had a significant dose-dependent influence on stool consistency ( 0.8 g/dL versus placebo , P < 0.0001 ; 0.8 g/dL versus 0.4 g/dL , P < 0.01 ) . Supplementation had no influence on the incidence of side effects ( crying , regurgitation , vomiting ) or growth . Conclusions These data indicate that supplementation of a term infant 's formula with a mixture of galacto- and fructooligosaccharides has a dose-dependent stimulating effect on the growth of Bifidobacteria and Lactobacilli in the intestine and results in softer stool with increasing dosage of supplementation 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 Objectives : To come even closer to the functional composition of human milk , acidic oligosaccharides ( AOS ) from pectin were added to well known neutral prebiotics ( galacto-oligosaccharides ( GOS ) and long-chain fructo-oligosaccharides ( FOS ) ) . The effect of AOS and GOS/FOS/AOS on intestinal flora , stool characteristics as well as acceptance and tolerance was investigated . Methods : Human milk contains 75 % to 85 % neutral and 15 % to 25 % acidic oligosaccharides . In this prospect i ve , r and omized , double blind study , a mixture of 80 % neutral oligosaccharides ( from long-chain galacto- and long-chain fructo-oligosaccharides ) with 20 % acidic oligosaccharides derived from pectin hydrolysis was investigated . Forty-six term infants were fed a st and ard formula supplemented with either maltodextrin as control ( n = 15 ) , or with 0.2 g acidic oligosaccharides ( n = 16 ) , or with the latter plus 0.6 g neutral oligosaccharides ( mixture of galacto- and fructo-oligosaccharides ; n = 15 ) . Fecal flora using plating technique and pH were measured . Stool characteristics and possible side effects ( crying , vomiting , and regurgitation ) were recorded . Results : There was no difference in the bifidobacteria counts between the control and the group supplemented with acidic oligosaccharides alone ( 8.75 ± 0.50 vs. 8.58 ± 0.94 log colony forming units [CFU]/g stool ) . In infants fed the combination of acidic and neutral oligosaccharides , bifidobacteria were increased ( 9.61 ± 0.70 log CFU/g stool ; P < 0.01 ) . The same pattern was observed with lactobacilli . Stool consistency was softest in infants fed the complete oligosaccharide mixture , but also in those fed formula supplemented with acidic oligosaccharides alone , the stool consistency was significantly softer compared with the control group . Fecal pH increased in the controls , remained constant in acidic oligosaccharides alone , and decreased in the complete mixture of oligosaccharides group . Conclusion : There was no difference in growth , crying , vomiting , and regurgitation patterns between the groups . In summary , acidic oligosaccharides from pectin hydrolysate are well tolerated as ingredient in infant formulae but do not affect intestinal microecology Background : The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant . Objective : To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants . Study design : To resemble the effect of human milk , an oligosaccharide mixture consisting of 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides was used to supplement a st and ard preterm formula at a concentration of 10 g/l . This supplemented formula was studied in 15 preterm infants , and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo .  A group fed fortified mother 's milk  was investigated as a reference group ( n = 12 ) . On four days during a 28 day feeding period ( 1 , 7 , 14 , and 28 ) , the faecal flora was investigated , and stool characteristics , growth , and possible side effects were recorded . Results : During the study period , the number of bifidobacteria in the group fed the oligosaccharide supplemented formula increased to the upper range of bifidobacteria counts in the reference group . The difference between the supplemented and non-supplemented groups was highly significant ( p = 0.0008 ) . The stool characteristics were also influenced by the supplement : the stool frequency after 28 days was significantly lower in the control group than in the oligosaccharide supplemented group ( p = 0.0079 ) and the reference group ( p < 0.0001 ) . Over the study period , the stool consistency in the control group became harder , but remained fairly stable in the other two groups . There was no effect of the different diets on the incidence of side effects ( crying , regurgitation , vomiting ) or on weight gain or length gain . Conclusion : Supplementing preterm formula with a mixture of galacto- and fructo-oligosaccharides at a concentration of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in stool characteristics similar to those found in preterm infants fed human milk . Therefore prebiotic mixtures such as the one studied may help to improve intestinal tolerance to enteral feeding in preterm infants AIM To investigate the effect of a new infant formula supplemented with a low level ( 0.24 g/100 mL ) of galacto-oligosaccharide ( GOS ) on intestinal micro-flora ( Bifidobacteria , Lactobacilli and E. coli ) and fermentation characteristics in term infants , compared with human milk and a st and ard infant formula without GOS . METHODS Term infants ( n = 371 ) were approached in this study in three hospitals of China . All infants started breast-feeding . Those who changed to formula-feeding within 4 wk after birth were r and omly assigned to one of the two formula groups . Growth and stool characteristics , and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period . Fecal sample s were collected from a sub population of recruited infants for analysis of intestinal bacteria ( culture technique ) , acetic acid ( gas chromatography ) and pH ( indicator strip ) . RESULTS After 3 mo , the intestinal Bifidobacteria , Lactobacilli , acetic acid and stool frequency were significantly increased , and fecal pH was decreased in infants fed with the GOS-formula or human milk , compared with those fed with the formula without GOS . No significant differences were observed between the GOS formula and human milk groups . Supplementation with GOS did not influence the incidence of crying , regurgitation and vomiting . CONCLUSION A low level of GOS ( 0.24 g/100 mL ) in infant formula can improve stool frequency , decrease fecal pH , and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk This study was conducted at Pakkred Babies Home , Bangkok , Thail and ; with the hypothesis that children receiving probiotic-supplemented milk-based formula  may be protected from developing diarrheal diseases . Salivary rotavirus-specific IgA antibody was used as an indicator of rotavirus infection . One hundred and seventy-five children , aged 6 - 36 months , were enrolled in the study . They were divided into 3 groups according to the type of formula given . There were 81 episodes of diarrhea during an 8-month study period , most of which were caused by bacterial enteropathogens . Ninety-seven pairs of salivary sample s were adequate for the analysis of rotavirus antibody . Among 23 children receiving milk-based follow-up formula and serving as control group , 30.4 per cent of them had > or = 4-fold increase in the antibody titre , indicating sub clinical rotavirus infection . The majority of children in the other 2 study groups , receiving the same formula supplemented with either Bifidobacterium Bb12 alone or together with Streptococcus thermophilus , had no significant change in the antibody titres between the two time points . The results of this study support our hypothesis that children receiving bifidobacteria-supplemented milk-based formula may be protected against symptomatic rotavirus infection 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 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 Objectives Probiotics may be useful in preventing acute infectious diarrhea .  Bifidobacteria are particularly attractive as probiotics agent because they constitute the predominant colonic flora of breastfed infants and are thought to play a role in the decreased incidence of diarrhea in breastfed infants . Methods This was a multicenter , double-blind , controlled study to evaluate the efficacy of a milk formula supplemented with viable Bifidobacterium lactis strain Bb 12 ( BbF ) in the prevention of acute diarrhea in infants younger than 8 months living in residential nurseries or foster care centers . Results Ninety healthy children received either the BbF or a conventional formula ( CF ) daily . The mean duration of the stay in the residential center was similar ( 137 v 148 days ) . At enrollment , there were no differences between the two groups with respect to age ( 3.7 ± 2.1 months ) , gender , anthropometric data , history of allergy or gastrointestinal disease , frequency of breast-feeding in the neonatal period or timing of introduction of solid food . Altogether , 28.3 % of the BbF infants  had diarrhea during the study compared with 38.7 % of controls ( NS ) . There was a statistically insignificant trend for shorter episodes of diarrhea in the BbF group ( 5.1 ± 3.3 days v 7 ± 5.5 days , NS ) . The number of days with diarrhea was 1.15 ± 2.5 in the BbF group with a daily probability of diarrhea of 0.84 versus 2.3 ± 4.5 days and 1.55 , respectively , in the CF group ( P = 0.0002 and 0.0014 ) . Feeding infants with the BbF reduced their risk of getting diarrhea by a factor of 1.9 ( range , 1.33–2.6 ) . Analysis of the cumulative incidence of diarrheal episodes showed a trend that the first onset of diarrhea occurred later in the BbF group . Conclusion These results provide some evidence that viable Bifidobacterium lactis strain Bb 12 , added to an acidified infant formula , has some protective effect against acute diarrhea in healthy children Objective : To compare the safety and tolerance of two formulas , supplemented with different probiotic agents , in early infancy . Design : Prospect i ve r and omized placebo-controlled trial . Setting : Clinics of a University Medical Center . Subjects : Full-term healthy infants aged less than 4 months . Intervention : Infants were r and omly assigned for 4 weeks to a st and ard milk-based formula supplemented with either Bifidobacterium lactis ( BB-12 ) , Lactobacillus reuteri ( ATCC 55730 ) or a probiotics-free formula . Measures of Outcome : Growth parameters , daily characteristics of feeding , stooling and behavior , and side effects . Results : Fifty-nine infants , aged 3–65 days , were included . Subjects in all three groups were similar at entry in terms of gestational age , birth weight , sex , growth parameters and breast feeding rate prior to the study . The supplemented formulas were well accepted and did not reveal any adverse effects . A comparison of growth parameters , and variables of feeding , stooling and crying and irritability did not reveal any significant differences between groups . Conclusions : The use of formula supplemented with either Lactobacillus reuteri or Bifidobacterium lactis in early infancy , was safe , well tolerated and did not adversely affect growth , stooling habits or infant behavior We assessed the growth , tolerance , and acceptability as well as fecal flora composition and stool pH of 20 healthy full-term infants fed with a fermented whey-adapted infant formula containing viable bifidobacteria ( 10(6)/g of powder ) during the first 2 months of life . This fermented infant formula , first biologically acidified by Streptococcus thermophilus and Lactobacillus helveticus , was compared to a whey-adapted , nonacidified , low-phosphate infant formula in a double-blind , r and omized controlled study . The results were compared to a control group ( n = 14 ) of fully breast-fed infants . The fermented whey-adapted formula containing viable bifidobacteria induced a prevalence of colonization with bifidobacteria at 1 month of age similar to that of breast-fed infants ( 12/20 versus 8/14 ) but significantly higher than in the group fed the st and ard infant formula ( 4/20 ) . The mean bacterial count of bifidobacteria was similar in all colonized infants ; however , fecal pH was significantly lower in the breast-fed infants than in the nonacidified bottle-fed infants . This kind of infant formula was well tolerated and promoted a normal growth during the first 2 months 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 Goals : This clinical trial was carried out to determine whether oral treatment with a commercial probiotic formula containing Bifidobacterium lactis and Streptococcus thermophilus would reduce the frequency of  antibiotic-associated diarrhea ( AAD ) in infants . Study : In this double-bind formula controlled study , 80 infants , 6 to 36 months of age , were r and omly assigned to receive a commercial formula containing 107 viable cells of B. lactis and 106viable cells of S. thermophilus at the initiation of antibiotics for a duration of 15 days . The infants were assessed daily for formula intake , stool frequency , and stool consistency for a total duration of 30 days . Seventy-seven infants received  nonsupplemented formula for the entire duration . Results : There was a significant difference in the incidence of AAD in the children receiving probiotic-supplemented formula ( 16 % ) than nonsupplemented formula ( 31 % ) . Conclusions : The present study shows that prevention against AAD in infants was obtained by oral treatment with daily dose of B. lactis and S. thermophilus BACKGROUND Probiotic bacteria have beneficial effects on the immune system and gastrointestinal tract , but the impacts of their long-term consumption on health and growth in early infancy are not well documented . The aim of this study was to evaluate the influence of Lactobacillus rhamnosus GG (LGG)-enriched formula on growth and faecal microflora during the first 6 months of life in normal healthy infants . MATERIAL S AND METHODS One hundred and twenty healthy infants ( up to 2 months ) received LGG-supplemented formula or regular formula in a double-blind , r and omized manner until the age of 6 months . Weight , length and head circumference were measured monthly and transformed into st and ard deviation scores ( SDS ) . Faecal sample s were obtained from a r and om sample of infants ( n=25 ) at entry and at the end of the study . RESULTS One hundred and five infants ( 51 in the LGG group ) completed the study . Children receiving LGG-supplemented formula grew better : their changes in their length and weight SDS ( DeltaSDS ) at the end of the study were significantly higher than those receiving regular formula ( 0.44+/- 0.37 versus 0.07+/- 0.06 , P < 0.01 and 0.44+/- 0.19 versus 0.07+/- 0.06 , P < 0.005 , respectively ) . The LGG group had a significant , higher defecation frequency 9.1+/-2.06 versus 8.0+/- 2.8 ( P<0.05 ) . More frequent colonization with lactobacilli was found in the LGG group , 91 % versus 76 % ( P<0.05 ) at the end of the study . CONCLUSIONS Infants fed with LGG-enriched formula grew better than those fed with regular formula . Further studies are necessary to clarify the mechanism of LGG in infant growth 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 OBJECTIVES The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants . We assessed the safety and tolerability of an experimental formula containing 2 x 10(7 ) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides . METHODS A 7-mo prospect i ve , r and omized , reference-controlled , double-blinded trial was performed in infants who were not breast fed after the 14th day of birth . One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old .  Mean weight gain ( primary outcome ) and recumbent length , head circumference , tolerability ( gastrointestinal symptoms ) , and overall morbidity ( secondary outcomes ) were measured at 14 , 28 , 56 , 84 , and 112 d of age . RESULTS Equivalence in mean weight gain between the two groups was shown . The treatment difference in the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d . No statistically significant difference in recumbent length , head circumference , or incidence of adverse events was found between the two groups . Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well . Furthermore , these infants showed a trend toward fewer respiratory tract infections . CONCLUSIONS The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated The aim of the study was to evaluate whether supplementation of milk-formulas with prebiotic fructo-oligosaccharides or a probiotic , Lactobacillus johnsonii La1 ( La1 ) , could modulate the composition of the fecal microbiota of formula-fed infants , compared to breastfed ( BF ) infants . Ninety infants close to 4 months of age were r and omized into one of three groups to be blindly assigned to receive for 13 weeks : a ) an infant formula ( Control ) , b ) the same formula with fructo-oligosaccharides ( Prebio ) , or c ) with La1 ( Probio ) . At the end of this period , all infants received the control formula for 2 additional weeks . Twenty-six infants , breastfed throughout the study , were recruited to form group BF . Fecal sample s were obtained upon enrolment and after 7 and 15 weeks . Bacterial population s were assessed with classical culture techniques and fluorescent in situ hybridisation ( FISH ) . Seventy-six infants completed the study . On enrolment , higher counts of Bifidobacterium and Lactobacillus and lower counts of enterobacteria were observed in BF compared to the formula-fed infants ; these differences tended to disappear at weeks 7 and 15 . No major differences for Clostridium , Bacteroides or Enterococcus were observed between the groups or along the follow up . Probio increased fecal Lactobacillus counts ( p<0.001 ) ; 88 % of the infants in this group excreted live La1 in their stools at week 7 but only 17 % at week 15 . Increased Bifidobacterium counts were observed at week 7 in the 3 formula groups , similar to BF infants . These results confirm the presence of higher counts of bifidobacteria and lactobacilli in the microbiota of BF infants compared to formula-fed infants before dietary diversification , and that La1 survives in the infant digestive tract BACKGROUND Oligosaccharides in human milk may protect infants by improving the intestinal micro-flora and fermentation . This study was to investigate effects of  infant formula milk consisting of galacto-oligosaccharide ( GOS ) on intestinal microbial population s and the fermentation characteristics in term infants in comparison with that of human milk . METHODS The test formula ( Frisolac H , Friesl and , Netherl and ) was supplemented with GOS at a concentration of 0.24 g/dl . Human milk and another formula without oligosaccharides ( Frisolac H , Friesl and , Netherl and ) were used as positive and negative control respectively . Growth , stool characteristics , and side effects of the recruited infants were recorded after 3 and 6 months ' follow-up , and the fecal species were collected for the analysis of intestinal micro-flora , short chain fatty acid ( SCFA ) and pH. RESULTS At the end of 3- and 6-month feeding period , intestinal Bifidobacteria and Lactobacilli were significantly increased in infants fed with GOS supplemented formula and human milk when compared with infants fed with negative control formula ; however , there was no statistically significant difference between GOS supplemented formula and human milk groups . Stool characteristics were influenced by the supplement and main fecal SCFA ( acetic ) , and stool frequency were significantly increased in infants fed with GOS supplemented formula and human milk , while the fecal pH was significantly decreased as compared with that of negative control ( P < 0.05 ) . Supplementation had no influence on incidence of side effects ( including crying , regurgitation and vomiting ) . CONCLUSIONS Supplementing infant formula with GOS at a concentration of 0.24 g/dl stimulates the growth of Bifidobacteria and Lactobacilli in the intestine and stool characteristics are similar to in term infants fed with human milk BACKGROUND The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various compounds of breast milk including prebiotic substances . AIM This prospect i ve , double blind , study compared the growth , acceptability and the proportion of bifidobacteria and clostridia in the stool flora of bottle-fed infants r and omized to receive a formula with a specific mixture of 0.4 g/100 ml prebiotic galacto- and long-chain fructooligosaccharides or the same formula without added prebiotics . METHODS Within 0 - 14 days after birth at term , healthy bottle-fed infants were enrolled to receive either a prebiotic formula or a st and ard formula . At recruitment anthropometric measurements were done . These were repeated at the age of 6 and 12 weeks . Stool sample s were taken at inclusion and at the age of 6 weeks . The number of bifidobacteria and clostridia was determined by fluorescent in situ hybridization . RESULTS There was good tolerance of the prebiotic formula . Somatic growth was similar in the two groups . Stool frequency was significantly higher in the prebiotic group ( P=0.031 ) . Infants in the prebiotic group had also softer stools as compared to the control group ( P=0.026 ) . Baseline values of microorganisms at study entry were similar . The percentage of faecal clostridia at the completion of the study was significantly lower in the prebiotic group ( P=0.042 ) , while the proportion of faecal bifidobacteria was higher in the prebiotic group as compared to the control group . However this difference did not reach statistical significance ( P=0.262 ) . The percentage of E. coli was lower in the prebiotic group but again this did not reach statistical significance ( P=0.312 ) . CONCLUSION An infant formula containing prebiotic oligosaccharides is well tolerated , leads to normal somatic growth and suppresses the numbers of clostridia in the faeces with a trend for higher percentage of stool bifidobacteria and lower percentage of E. coli 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 A double‐blind , r and omized , controlled study was performed in 90 full term infants to evaluate dose‐related bifidogenic effects of a new synergistic mixture of galacto‐oligosaccharides ( GOS ) and fructo‐oligosacharides ( FOS ) . The GOS/FOS mixture showed a dose‐dependent stimulatory effect on the intestinal growth of bifidobacteria . Also stool consistency and faecal pH were positively affected Objectives : The present study was design ed to evaluate the effect of 2 different combinations of prebiotic ingredients , polydextrose ( PDX ) , galactooligosaccharides ( GOS ) , and lactulose ( LOS ) , at 2 different intake levels on the overall growth and tolerance in healthy term infants up to 120 days of age . Patients and Methods : Healthy , formula-fed , term infants ( n = 226 ) were r and omly assigned to 1 of 3 study formula groups : control group ( n = 76 ) , PG4 group ( control formula supplemented with 4 g/L of a prebiotic blend , n = 74 ) , or PGL8 group ( control formula supplemented with 8 g/L of a prebiotic blend , n = 76 ) . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age , and 24-hour dietary recall and 24-hour tolerance recall were recorded at 30 , 60 , 90 , and 120 days of age . Adverse events were recorded throughout the study . Results : There were no statistically significant differences among the 3 formula groups for weight growth rate or length growth rate at any time point . Significant differences in stool consistency were detected among the 3 formula groups at 30 , 60 , and 90 days of age ( P < 0.001 , P = 0.025 , P = 0.004 , respectively ) , with the supplemented formula groups having looser stools than the control group . The PGL8 group had significantly higher stool frequency compared with the control and PG4 groups at 30 days of age ( P = 0.021 and P = 0.017 , respectively ) , but all of the groups were similar at 60 , 90 , and 120 days of age . A statistical difference was detected among the formula groups in 3 categories of adverse events : diarrhea ( control vs PG4 , 4 % vs 18 % , P = 0.008 ) , eczema ( PG4 vs control , 18 % vs 7 % , P = 0.046 ; PG4 vs PGL8 , 18 % vs 4 % , P = 0.008 ) , and irritability ( control vs PGL8 , 4 % vs 16 % , P = 0.027 ) . Conclusions : Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants in comparison with infants fed an unsupplemented formula . A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics Acute diarrhea is a common cause of infant morbidity and mortality . Probiotic supplemented infant formula is one of the effective methods for prevention of rotavirus diarrhea . Other benefits of the probiotics supplemented formula were evaluated by monitoring the growth of the children . A double-blind , placebo-controlled trial was done in 148 children aged 6 - 36 months . They were divided into 3 groups : the Bb12 group , 51 children received infant formula with Bifidobacteria Bb12 supplement ; the Bb12+ST  group , 54 children  received infant formula with Bb12 and Streptococcus thermophilus supplement ; and the control group , 43 children received infant formula without supplement . The mean weight Z-score according to WHO reference st and ard of the Bbl2 group was -1.8 + /- 0.12 , the Bb12+ST group was -1.4 + /- 0.11 and the control group was -1.8 + /- 0.13 at entry . The mean weight Z-score of children after 6 month showed that the children in the Bbl2+ST group had the highest increase in weight which was increased from -1.4 + /- 0.11 to -0.9 + /- 0.12 compared to the Z-score of the Bb12 group which had increased from -1.8 + /- 0.12 to -1.2 + /- 0.13 and in the control group from -1.8 + /- 0.13 to -1.7 + /- 0.25 . In terms of the mean height Z-score , the Bb12 group was -2.7 + /- 0.14 to -1.7 + /- 0.16 which was higher than the Bb12+ST group ( - 2.2 + /- 0.13 to -1.7 + /- 0.13 ) but was not different from the control group . However , the mean weight/height Z-score of the Bbl2+ST group had approached the reference st and ard ( Bb12 group -0.1 + /- 0.11 to -0.1 + /- 0.13 , Bb12+ST group -0.1 + /- 0.10 to 0.3 + /- 0.17 , control group -0.4 + /- 0.12 to -0.1 + /- 0.16 ) . Data showed that children who received the probiotics supplement formula had better growth during the 6 month period Secretory immunoglobulin A ( SIgA ) plays an important role in the defence of the gastrointestinal tract . The level of faecal SIgA antibody is associated with increased neutralization and clearance of viruses . Formula-fed infants who lack the transfer of protective maternal SIgA from breast milk may benefit from strategies to support maturation of humoral immunity and endogenous production of SIgA. We aim ed at study ing the effects of st and ard , prebiotic and probiotic infant formulas on the faecal SIgA levels . At birth , infants of whom the mother had decided not to breastfeed were allocated to one of three formula groups in a r and omized , double-blind fashion . Nineteen infants received st and ard infant formula ; 19 received prebiotic formula containing a specific mixture of 0.6 g galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and 19 received probiotic formula containing 6.0 x 10(9 ) cfu Bifidobacterium animalis/100 ml formula . Faecal sample s were taken on postnatal day 5 , day 10 , wk 4 and every 4 wk thereafter until wk 32 . SIgA in faeces was determined by an enzyme-linked immunosorbent assay . During the intervention , infants fed on prebiotic formula showed a trend towards higher faecal SIgA levels compared with the st and ard formula-fed infants reaching statistical significance at the age of 16 wk . In contrast , infants fed on the probiotic formula showed a highly variable faecal SIgA concentration with no statistically significant differences compared with the st and ard formula group . Formula-fed infants may benefit from infant formulas containing a prebiotic mixture of GOS and FOS because of the observed clear tendency to increase faecal SIgA secretion . Adding viable B. animalis strain Bb-12 to infant formula did not reveal any sign for such a trend Objective : To test the safety and effect on faecal microbiota of a formula with prebiotic oligosaccharides alone or in combination with acidic oligosaccharides in infants at the age of partial formula feeding . Patients and Methods : The study was a double-blind , placebo-controlled , r and omised intervention trial in which 82 healthy , full-term , partially breast-fed children , from 1 week to 3 months old , were given 1 of the following formulae : whey-based formula ( control group ) , whey-based formula with galacto- and long-chain fructo-oligosaccharides ( scGOS/lcFOS group ) , or whey-based formula with galacto- and long-chain fructo-oligosaccharides added with pectin-derived acidic oligosaccharides ( scGOS/lcFOS/pAOS group ) . Children were studied for the duration of the partial formula feeding period and every 2 weeks for 2 months after breast-feeding cessation . The total bacteria count and the proportion of 7 bacterial families were determined using in situ hybridisation coupled to flow cytometry . Results : The total bacterial count did not alter with time or type of feeding ( 9.9 ± 0.1 log10 cells per gram wet weight ) . Compared with the control group , there was an increase of the Bifidobacterium genus ( P = 0.0001 ) , and a decrease of proportions for the Bacteroides group ( P = 0.02 ) and the Clostridium coccoides group ( P = 0.01 ) in both oligosaccharide groups . The proportion of bifidobacteria was significantly higher in the scGOS/lcFOS/pAOS compared with the scGOS/lcFOS group ( P < 0.01 ) . Conclusions : Infant formulae appear to be clinical ly safe and effective on infant microbiota . They minimize the alteration of faecal microbiota after cessation of breast-feeding and promote bifidobacteria proportions , with a stronger effect when acidic oligosaccharides are present OBJECTIVE . Live probiotic bacteria and dietary prebiotic oligosaccharides ( together termed synbiotics ) increasingly are being used in infancy , but evidence of long-term safety is lacking . In a r and omized , placebo-controlled , double-blind trial , we studied the safety and long-term effects of feeding synbiotics to newborn infants . METHODS . Between November 2000 and March 2003 , pregnant mothers carrying infants at high risk for allergy were r and omly assigned to receive a mixture of 4 probiotic species ( Lactobacillus rhamnosus GG and LC705 , Bifidobacterium breve Bb99 , and Propionibacterium freudenreichii ssp shermanii ) or a placebo for 4 weeks before delivery . Their infants received the same probiotics with 0.8 g of galactooligosaccharides , or a placebo , daily for 6 months after birth . Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3 , 6 , and 24 months and from question naires at ages 3 , 6 , 12 , and 24 months . Growth data were collected at each time point . RESULTS . Of the 1018 eligible infants , 925 completed the 2-year follow-up assessment . Infants in both groups grew normally . We observed no difference in neonatal morbidity , feeding-related behaviors ( such as infantile colic ) , or serious adverse events between the study groups . During the 6-month intervention , antibiotics were prescribed less often in the synbiotic group than in the placebo group ( 23 % vs 28 % ) . Throughout the follow-up period , respiratory infections occurred less frequently in the synbiotic group ( geometric mean : 3.7 vs 4.2 infections ) . CONCLUSION . Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life Background / Aims : Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects . This study aim ed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii ( La1 ® ) .  Methods : In the framework of a double-blind , r and omized controlled trial enrolling 71 infants aged 4–5 months , morning urine sample s were collected before and 4 weeks after being fed formulas with or without La1  ( 1 × 108/g powder ) or being breastfed . Urinary D- and L-lactate concentrations were assayed by enzymatic , fluorimetric methods and excretion was normalized per mol creatinine . Results : At baseline , no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found . After 4 weeks , D-lactate excretion did not differ between the two formula groups , but was higher in both formula groups than in breastfed infants . In all infants receiving La1  , urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method . Urinary L-lactate also did not vary over time or among groups . Conclusions : Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis OBJECTIVE Cholesterol is a nutrient of essential importance in infant feeding because it is necessary in membrane development . In adults with high lipid levels , high doses of inulin ( oligofructose ) inconsistently decreased levels of serum cholesterol . The aim of the present study was to evaluate cholesterol and triacylglycerol levels in infants receiving a formula with a specific mixture of 0.6 g/100 mL of galacto-oligosaccharides ( GOS ) and long-chain fructo-oligosaccharides ( lcFOS ) in a ratio of 9/1 , a  control formula , or  breast milk .  Because the level of lcFOS in the infant milk is low , we hypothesized that there would be no differences between the formula groups . METHODS Two hundred fifteen infants were included in a prospect i ve , r and omized , double-blinded , placebo-controlled trial during the first 6 mo of life . Formula-fed infants were r and omized to receive a st and ard infant formula with a specific mixture of 0.6 g/100 mL of GOS/lcFOS , in a ratio of 9/1 , or a control formula .  Breast-fed infants were r and omized to receive one of these two formulas after the mother had decided to discontinue breastfeeding . Serum levels of cholesterol , high-density lipoprotein , low-density lipoprotein ( LDL ) , and triacylglycerol were determined at 8 and 26 wk of age and were provided for infants who received the GOS/lcFOS formula or control formula from birth or after cessation of breastfeeding and for the subgroups that were fully fed with breast milk and formula . RESULTS One hundred eighty-seven infants completed the study .  Total cholesterol and LDL levels at 8 and 26 wk were significantly lower in the formula-fed groups than in the breast-fed infants . There were no significant differences between the formula-fed groups . Levels of triacylglycerols and high-density lipoprotein did not differ between groups . CONCLUSION Our study demonstrated no differences in total cholesterol and LDL cholesterol in infants receiving an infant formula with GOS/lcFOS from infants receiving a control infant formula . Furthermore , total cholesterol and LDL cholesterol levels were higher in breast-fed infants than in formula-fed infants Acute diarrhoea is a serious cause of infant morbidity and mortality , and the development of preventive measures remains an important goal . Bifidobacteria ( which constitute the predominant intestinal flora of breastfed infants ) , as well as other lactic-acid-producing organisms such as Streptococcus thermophilus , are thought to have a protective effect against acute diarrhoeal disease . However , their efficacy has not been assessed in controlled trials . In a double-blind , placebo-controlled trial , infants aged 5 - 24 months who were admitted to a chronic medical care hospital were r and omised to receive a st and ard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus . Patients were evaluated daily for occurrence of diarrhoea , and faecal sample s , obtained weekly , were analysed for rotavirus antigen by enzyme immunoassay . Faecal sample s were also obtained during an episode of diarrhoea for virological and bacteriological analyses . 55 subjects were evaluated for a total of 4447 patient-days during 17 months . 8 ( 31 % ) of the 26 patients who received the control formula and 2 ( 7 % ) of 29 who received the supplemented formula developed diarrhoea during the course of the study ( p = 0.035 , Fisher 's exact test , two-tailed ) . 10 ( 39 % ) of the subjects who received the control formula and 3 ( 10 % ) of those who received the supplemented formula  shed rotavirus at some time during the study ( p = 0.025 ) . The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital Healthy , term infants received extensively hydrolyzed casein formula ( EHF ; control ) , the same formula supplemented with Lactobacillus rhamnosus GG ( EHF-LGG ) , or partially hydrolyzed whey : casein ( 60:40 ) formula supplemented with LGG ( PHF-LGG ) , in this double-blind , r and omized , controlled , parallel , prospect i ve study . Anthropometric measures and 24-hour dietary and tolerance recalls were obtained at 30 , 60 , 90 , 120 , and 150 days of age . Blood collected in a subset of infants was analyzed for fatty acid profiles in plasma and red blood cells and for markers of allergic sensitization . Adverse events were recorded throughout the study . Growth rates were not statistically different between EHF and PHF-LGG and between EHF and EHF-LGG from day 14 to day 30 , 120 , or 150 . No relevant differences in formula tolerance , adverse events , or allergic and immune markers were demonstrated between groups . The extensively and partially hydrolyzed formulas supplemented with LGG support normal growth in healthy , term infants and are well tolerated and safe OBJECTIVE Intestinal microbiota plays an important role in the prevention of certain diseases during the pediatric years . Thus , there is an increasing interest in the addition of probiotics to infant formulas . The aim of this study was to evaluate the safety of a follow-on formula with Lactobacillus salivarius CECT5713 in 6-mo-old children . METHODS The antibiotic susceptibility of L. salivarius CECT5713 was analyzed by a dilution method . A double-blinded , r and omized , placebo controlled study was performed . Children ( n = 80 ) were distributed in two groups and consumed the formula supplemented or not with probiotics ( 2 × 10(6 ) colony-forming units [cfu]/g ) during 6 mo . Fecal sample s were collected at enrollment , at 3 mo , and at the end of trial . Clinical and anthropometric evaluations were performed . Depending on the variable , one-way or two-way repeated measures analysis of variance were used for the statistical analysis . RESULTS The antibiotic susceptibility profile of the strain result ed as safe . No adverse effects associated with the consumption of the probiotic formula were reported . In addition , clinical parameters did not differ between groups . Consumption of the probiotic supplemented formula led to an increase in the fecal lactobacilli content ( 7.6 ± 0.2 versus 7.9 ± 0.1 log cfu/g , P < 0.05 ) . Lactobacillus salivarius CECT5713 was detected in the feces of volunteers from the probiotic group . Probiotic consumption induced a significant increase in the fecal concentration of butyric acid at 6 mo . CONCLUSION Thus , a follow-on formula with L. salivarius CECT5713 is safe and well tolerated in 6-mo-old infants
target: On the basis of this review , available scientific data suggest that the administration of currently evaluated probiotic- and /or prebiotic-supplemented formula to healthy infants does not raise safety concerns with regard to growth and adverse effects .
background: Infant formulae are increasingly supplemented with probiotics , prebiotics , or synbiotics despite uncertainties regarding their efficacy .
  The present article , developed by the Committee on Nutrition of the European Society for Paediatric Gastroenterology , Hepatology , and Nutrition , systematic ally review s published evidence related to the safety and health effects of the administration of formulae supplemented with probiotics and /or prebiotics compared with unsupplemented formulae .