Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. Specific probiotics in enhancing maturation of IgA responses in formula-fed infants. Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics. Probiotics during pregnancy and breast-feeding might confer immunomodulatory protection against atopic disease in the infant. Effects of probiotic or prebiotic supplemented milk formulas on fecal microbiota composition of infants. Growth during the first 6 months of life in infants using formula enriched with Lactobacillus rhamnosus GG: double-blind, randomized trial. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants.
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.
                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.
                This was a prospective, double-blind, randomized, placebo-controlled study of healthy infants aged 3-24 mo. Infants were assigned to receive a standard 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.
                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.
                Long-term consumption of formulas supplemented with B. lactis and S. thermophilus was well tolerated and safe and resulted in adequate growth, reduced reporting of colic or irritability, and a lower frequency of antibiotic use. 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.
                We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases.
                We randomized 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.
                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.
                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.
                The prevention of atopic eczema in high-risk infants is possible by modulating the infant's gut microbiota with probiotics and prebiotics. 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).
                In a double-blind, randomised 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.
                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).
                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. To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense, thereby reducing both the incidence and severity of necrotizing enterocolitis (NEC) in preterm neonates.
                Neonates < or =1500 g birth weight were randomized to either receive a daily feeding supplementation with a probiotic mixture (Bifidobacteria infantis, Streptococcus thermophilus, and Bifidobacteria bifidus; Solgar, Israel) of 10(9) colony forming units (CFU)/day or to not receive feed supplements. NEC was graded according to Bell's criteria.
                For 72 study and 73 control infants, respectively, birth weight (1152 +/- 262 g vs 1111 +/- 278 g), gestational age (30 +/- 3 weeks vs 29 +/- 4 weeks), and time to reach full feeds (14.6 +/- 8.7 days vs 17.5 +/- 13.6 days) were not different. The incidence of NEC was reduced in the study group (4% vs 16.4%; P=.03). NEC was less severe in the probiotic-supplemented infants (Bell's criteria 2.3 +/- 0.5 vs 1.3 +/- 0.5; P=.005). Three of 15 babies who developed NEC died, and all NEC-related deaths occurred in control infants.
                Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population. Despite preliminary evidence, the role of probiotics in allergy prevention is unclear.
                To determine whether early probiotic supplementation prevents allergic disease in high-risk infants.
                Newborns of women with allergy (n = 231) received either Lactobacillus acidophilus (LAVRI-A1) or placebo daily for the first 6 months of life. Children were assessed for atopic dermatitis (AD) and other symptoms at 6 and 12 months and had allergen skin prick tests (SPT) at 12 months of age.
                A total of 178 infants completed the supplementation period. Those in the probiotic group showed significantly higher rates of Lactobacillus colonization (P = .039). At 6 months, AD rates were similar in the probiotic (n = 23/89; 25.8%) and placebo (n = 20/88; 22.7%) groups (P = .629). There was also no difference at 12 months, although the proportion of children with SPT+AD was significantly higher in the probiotic group (P = .045). At 12 months, the rate of sensitization was significantly higher in the probiotic group (P = .030). The presence of culturable Lactobacilli or Bifidobacterium in stools in the first month of life was not associated with the risk of subsequent sensitization or disease; however, the presence of Lactobacillus at 6 months of age was associated with increased risk of subsequent cow's milk sensitization (P = .012).
                Early probiotic supplementation with L acidophilus did not reduce the risk of AD in high-risk infants and was associated with increased allergen sensitization in infants receiving supplements. The long-term significance of the increased rate of sensitization needs to be investigated in further studies.
                These findings challenge the role of probiotics in allergy prevention. The first months of life represent a critical period for the maturation of the infant's immune system and, thus, a window of opportunity for measures to reduce the risk of disease. We hypothesized that specific probiotics might promote mucosal immunologic maturation in formula-fed infants. The numbers of cow's milk-specific and total IgA-secreting cells were measured at 3, 7, and 12 mo of age in a double-blind placebo-controlled study of 72 infants with early artificial feeding. The infants consumed infant formula supplemented with specific probiotics (Lactobacillus GG and Bifidobacterium lactis Bb-12) or placebo during the first year of life. Further analyses of the serum concentrations of the IgA-inducing cytokine TGF-beta2 and the soluble innate microbial receptor sCD14 were conducted. The numbers of cow's milk-specific IgA secreting cells were significantly higher in infants receiving probiotics compared with those receiving placebo (p = 0.045, ANOVA for repeated measures). At 12 mo of age, the serum concentrations of sCD14 were 1479 pg/mL [95% confidence interval (CI) 1373-1592] in infants receiving probiotics and 1291 pg/mL (95% CI 1152-1445) in infants receiving placebo (p = 0.046). Administration of the probiotics Lactobacillus GG and Bifidobacterium lactis Bb-12 at the time of introduction of cow's milk in the infant's diet results in cow's milk-specific IgA antibody responsiveness that may be the result of increased production of sCD14. 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.
                A 7-mo prospective, randomized, 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.
                Equivalence in mean weight gain between the two groups was shown. The treatment difference in the intention-to-treat and per-protocol populations 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.
                The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated. The prevalence of atopic diseases is increasing throughout the Western world, and means of primary prevention are needed to reverse this trend. The role of breast-feeding, the best source of infant nutrition, in protection against atopic disease remains elusive. In this double-blinded, placebo-controlled study of 62 mother-infant pairs, it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk, as assessed by the amount of anti-inflammatory transforming growth factor beta2 (TGF-beta2) in the milk (2885 pg/mL [95% CI, 1624-4146] in mothers receiving probiotics vs 1340 pg/mL [95% CI, 978-1702] in mothers receiving placebo; P =.018). The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo (15% and 47%, respectively; relative risk, 0.32 [95% CI, 0.12-0.85]; P =.0098). Maternal atopy was a clear risk factor for atopic eczema in the infant. The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration. Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life. The 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 randomized 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 samples were obtained upon enrolment and after 7 and 15 weeks. Bacterial populations 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. 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.
                One hundred and twenty healthy infants (up to 2 months) received LGG-supplemented formula or regular formula in a double-blind, randomized manner until the age of 6 months. Weight, length and head circumference were measured monthly and transformed into standard deviation scores (SDS). Faecal samples were obtained from a random sample of infants (n=25) at entry and at the end of the study.
                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. We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants.
                A prospective, masked, randomized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW (<1500 g) infants. VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial. They were randomized into 2 groups after parental informed consents were obtained. The infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharged. Infants in the control group were fed with breast milk alone. The clinicians caring for the infants were blinded to the group assignment. The primary outcome was death or NEC (>or= stage 2).
                Three hundred sixty-seven infants were enrolled: 180 in the study group and 187 in the control group. The demographic and clinical variables were similar in both groups. The incidence of death or NEC (>or= stage 2) was significantly lower in the study group (9 of 180 vs 24 of 187). The incidence of NEC (>or= stage 2) was also significantly lower in the study when compared with the control group (2 of 180 vs 10 of 187). There were 6 cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood culture grew Lactobacillus or Bifidobacterium species.
                Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants.
There is insufficient evidence to recommend the addition of probiotics to infant feeds for prevention of allergic disease or food hypersensitivity. Although there was a reduction in clinical eczema in infants, this effect was not consistent between studies and caution is advised in view of methodological concerns regarding included studies. Further studies are required to determine whether the findings are reproducible.