Gut microbiota analysis reveals a marked shift to bifidobacteria by a starter infant formula containing a synbiotic of bovine milk-derived oligosaccharides and Bifidobacterium animalis subsp. lactis CNCM I-3446.

Non-digestible milk oligosaccharides were proposed as receptor decoys for pathogens and as nutrients for beneficial gut commensals like bifidobacteria. Bovine milk contains oligosaccharides, some of which are structurally identical or similar to those found in human milk. In a controlled, randomized double-blinded clinical trial we tested the effect of feeding a formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS) generated from whey permeate, containing galacto-oligosaccharides and 3'- and 6'-sialyllactose, and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446. Breastfed infants served as reference group. Compared with a non-supplemented control formula, the test formula showed a similar tolerability and supported a similar growth in healthy newborns followed for 12 weeks. The control, but not the test group, differed from the breast-fed reference group by a higher faecal pH and a significantly higher diversity of the faecal microbiota. In the test group the probiotic B. lactis increased by 100-fold in the stool and was detected in all supplemented infants. BMOS stimulated a marked shift to a bifidobacterium-dominated faecal microbiota via increases in endogenous bifidobacteria (B. longum, B. breve, B. bifidum, B. pseudocatenulatum)

Stimulation of Interleukin-10 Production by Acidic β-Lactoglobulin-Derived Peptides Hydrolyzed with Lactobacillus paracasei NCC2461 Peptidases

We have previously demonstrated that Lactobacillus paracasei NCC2461 may help to prevent cow's milk allergy in mice by inducing oral tolerance to β-lactoglobulin (BLG). To investigate the mechanisms involved in this beneficial effect, we examined the possibility that L. paracasei induces tolerance by hydrolyzing BLG-derived peptides and liberating peptides that stimulate interleukin-10 (IL-10) production. L. paracasei peptidases have been shown to hydrolyze tryptic-chymotryptic peptides from BLG, releasing numerous small peptides with immunomodulating properties. We have now shown that acidic tryptic-chymotryptic peptides stimulate splenocyte proliferation and gamma interferon (IFN-γ) production in vitro. Hydrolysis of these peptides with L. paracasei peptidases repressed the lymphocyte stimulation, up-regulated IL-10 production, and down-regulated IFN-γ and IL-4 secretion. L. paracasei NCC2461 may therefore induce oral tolerance to BLG in vivo by degrading acidic peptides and releasing immunomodulatory peptides stimulating regulatory T cells, which function as major immunosuppressive agents by secreting IL-10

Effect of maternal supplement beverage with and without probiotics during pregnancy and lactation on maternal and infant health: a randomized controlled trial in the Philippines

Abstract Background Adequate nutrition is essential during pregnancy and lactation to provide sufficient energy and nutrients to meet the nutritional requirements of the mother, fetus and infant. The primary objective of this study was to assess the effect of a maternal nutritional supplement enriched with probiotics during pregnancy and early lactation on the incidence of infant diarrhea. Methods Healthy, pregnant (24–28 weeks gestation) women were randomized 1:1:1 to receive either no supplement or two servings per day of an oral supplement (140 kcal/serving) providing 7.9 g protein, multivitamin/minerals, and enriched or not with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis, from the third trimester of pregnancy until at least 2 months post-delivery. Incidence of infant diarrhea until 12 months post-delivery was analyzed by Poisson regression. The effect on maternal health, fetal growth, and infant growth and morbidity were also evaluated and analyzed by ANOVA. Results A total of 208 mother/infant pairs were included in the analysis. No significant difference in the incidence of infant diarrhea was observed between the three study groups. The mean maternal weight gains at delivery were similar among groups, despite an increase in caloric intake in the supplemented groups. No statistically significant differences between groups were observed in incidence of pregnancy-related or fetal adverse outcomes. Mean weight-, length-, BMI- and head circumference-for-age z-scores were below the WHO median value for all groups. Post-hoc analysis to compare the effect of the combined supplement groups versus the no supplement group on infant growth parameters showed, at 12 months, that the combined supplemented group had gained statistically significant more weight (8.97 vs. 8.61 kg, p = 0.001) and height (74.2 vs. 73.4 cm, p = 0.031), and had a higher weight-for-age z-score (− 0.62 vs. -0.88, p = 0.045) than the no supplement group. Conclusions Maternal nutritional supplement with or without probiotics given during late pregnancy and early lactation was well tolerated and safe. Even though no difference in incidence of infant diarrhea was observed between the three groups, the analysis of the combined supplemented groups showed beneficial effects of maternal supplementation on infant weight and length gains at 12 months. Trial registration ClinicalTrial.gov: NCT01073033. Registered 17.02.2010

Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants

Objective This multicenter non-inferiority study evaluated the safety of infant formulas enriched with bovine milk fat globule membrane (MFGM) fractions. Methods Healthy, full-term infants ( n = 119) age ≤14 days were randomized to standard infant formula (control), standard formula enriched with a lipid-rich MFGM fraction (MFGM-L), or standard formula enriched with a protein-rich MFGM fraction (MFGM-P). Primary outcome was mean weight gain per day from enrollment to age 4 months (non-inferiority margin: –3.0 g/day). Secondary (length, head circumference, tolerability, morbidity, adverse events) and exploratory (phospholipids, metabolic markers, immune markers) outcomes were also evaluated. Results Weight gain was non-inferior in the MFGM-L and MFGM-P groups compared with the control group. Among secondary and exploratory outcomes, few between-group differences were observed. Formula tolerance rates were high (>94%) in all groups. Adverse event and morbidity rates were similar across groups except for a higher rate of eczema in the MFGM-P group (13.9% vs control [3.5%], MFGM-L [1.4%]). Conclusion Both MFGM-enriched formulas met the primary safety endpoint of non-inferiority in weight gain and were generally well tolerated, although a higher rate of eczema was observed in the MFGM-P group

Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants

Objective This multicenter non-inferiority study evaluated the safety of infant formulas enriched with bovine milk fat globule membrane (MFGM) fractions. Methods Healthy, full-term infants ( n = 119) age ≤14 days were randomized to standard infant formula (control), standard formula enriched with a lipid-rich MFGM fraction (MFGM-L), or standard formula enriched with a protein-rich MFGM fraction (MFGM-P). Primary outcome was mean weight gain per day from enrollment to age 4 months (non-inferiority margin: –3.0 g/day). Secondary (length, head circumference, tolerability, morbidity, adverse events) and exploratory (phospholipids, metabolic markers, immune markers) outcomes were also evaluated. Results Weight gain was non-inferior in the MFGM-L and MFGM-P groups compared with the control group. Among secondary and exploratory outcomes, few between-group differences were observed. Formula tolerance rates were high (>94%) in all groups. Adverse event and morbidity rates were similar across groups except for a higher rate of eczema in the MFGM-P group (13.9% vs control [3.5%], MFGM-L [1.4%]). Conclusion Both MFGM-enriched formulas met the primary safety endpoint of non-inferiority in weight gain and were generally well tolerated, although a higher rate of eczema was observed in the MFGM-P group

Partially Hydrolyzed Whey Infant Formula: Literature Review on Effects on Growth and the Risk of Developing Atopic Dermatitis in Infants from the General Population.

Limited evidence is available regarding the effect of partially hydrolyzed whey-based formula (pHF-W) on growth and atopic dermatitis (AD) risk reduction in infants within the general infant population, and without a familial history of allergy as an inclusion or exclusion criterion. We reviewed the current evidence available from studies using pHF-W in the general population and summarized the data on safety (growth) and efficacy outcomes (reduction of AD), comparing the studies side by side. A total of 8 clinical trials were identified from the literature search, 7 of which used the same pHF-W. Six out of 8 studies indicated a reduction of atopic manifestations using a specific pHF-W versus cow's milk formula (CMF) in the first years of life. Data were summarized and compared side by side for growth (3 studies) and efficacy (5 studies). In these diverse general populations, the results on growth and AD were consistent with the previous findings reported on infants with a family history of allergy, but numerous limitations to these studies were identified. This literature review confirms that pHF-W supports normal growth in infants, and suggests that the risk of AD may be reduced in not-fully breastfed infants from the general population when supplemented with a specific pHF-W when compared to CMF during the first 4-6 months of life. Further studies are warranted to confirm these results

Early Benefits of a Starter Formula Enriched in Prebiotics and Probiotics on the Gut Microbiota of Healthy Infants Born to HIV+ Mothers: A Randomized Double-Blind Controlled Trial

The gut microbiota of infants is shaped by both the mode of delivery and the type of feeding. The gut of vaginally and cesarean-delivered infants is colonized at different rates and with different bacterial species, leading to differences in the gut microbial composition, which may persist up to 6 months. In a multicenter, randomized, controlled, double-blind trial conducted in South Africa, we tested the effect of a formula supplemented with a prebiotic (a mixture of bovine milk-derived oligosaccharides [BMOS] generated from whey permeate and containing galactooligosaccharides and milk oligosaccharides such as 3′- and 6′-sialyllactose) and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446 on the bifidobacteria levels in the gut of infants born vaginally or via cesarean section in early life. Additionally, the safety of the new formulation was evaluated. A total of 430 healthy, full-term infants born to HIV-positive mothers who had elected to feed their child beginning from birth (≤3 days old) exclusively with formula were randomized into this multicenter trial of four parallel groups. A total of 421 infants who had any study formula intake were included in the full analysis set (FAS). The first two groups consisted of cesarean-delivered infants assigned to the Test formula (n = 92) (a starter infant formula [IF] containing BMOS at a total oligosaccharide concentration of 5.8 ± 1.0 g/100 g of powder formula [8 g/L in the reconstituted formula] + B. lactis [1 × 10 7 colony-forming units {cfu}/g]) or a Control IF (n = 101); the second two groups consisted of vaginally delivered infants randomized to the same Test (n = 115) or Control (n = 113) formulas from the time of enrollment to 6 months. The primary efficacy outcome was fecal bifidobacteria count at 10 days, and the primary safety outcome was daily weight gain (g/d) between 10 days and 4 months. At 10 days, fecal bifidobacteria counts were significantly higher in the Test formula than in the Control formula group among infants with cesarean birth (median [range] log: 9.41 [6.30–10.94] cfu/g versus 6.30 [6.30–10.51] cfu/g; P = 0.002) but not among those with vaginal birth (median [range] log: 10.06 [5.93–10.77] cfu/g versus 9.85 [6.15–10.79] cfu/g; P = 0.126). The lower bound of the two-sided 95% confidence interval of the difference in the mean daily weight gain between the Test and Control formula groups was more than –3 g/d in both the vaginally and cesarean-delivered infants, indicating that growth in the Test formula-fed infants was not inferior to that of Control formula-fed infants. At 10 days and 4 weeks, the fecal pH of infants fed the Test formula was significantly lower than in those fed the Control formula, irrespective of mode of delivery: for vaginal delivery: 4.93 versus 5.59; P < 0.001 (10 days) and 5.01 versus 5.71; P < 0.001 (4 weeks); for cesarean delivery: 5.14 versus 5.65, P = 0.009 (10 days) and 5.06 versus 5.75, P < 0.001 (4 weeks). At 3 months, this acidification effect only persisted among cesarean-born infants. IF supplemented with the prebiotic BMOS and probiotic B. lactis induced a strong bifidogenic effect in both delivering modes, but more explicitly correcting the low bifidobacteria level found in cesarean-born infants from birth. The supplemented IF lowered the fecal pH and improved the fecal microbiota in both normal and cesarean-delivered infants. The use of bifidobacteria as a probiotic even in infants who are immunologically at risk is safe and well tolerated

Growth of Infants Fed Formula with Evolving Nutrition Composition: A Single‐Arm Non‐Inferiority Study

The nutritional composition of human milk evolves over the course of lactation, to match the changing needs of infants. This single‐arm, non‐inferiority study evaluated growth against the WHO standards in the first year of life, in infants consecutively fed four age‐based formulas with compositions tailored to infants’ nutritional needs during the 1st, 2nd, 3rd–6th, and 7th–12th months of age. Healthy full‐term formula‐fed infants (n = 32) were enrolled at ≤14 days of age and exclusively fed study formulas from enrollment, to the age of four months. Powdered study formulas were provided in single‐serving capsules that were reconstituted using a dedicated automated preparation system, to ensure precise, hygienic preparation. The primary outcome was the weight‐for‐age z‐score (WAZ) at the age of four months (vs. non‐inferiority margin of −0.5 SD). Mean (95% CI) z‐scores for the WAZ (0.12 (−0.15, 0.39)), as well as for the length‐for‐age (0.05 (−0.19, 0.30)), weight‐for‐length (0.16 (−0.16, 0.48)), BMI‐for‐age (0.11 (−0.20, 0.43)), and head circumferencefor‐age (0.41 (0.16, 0.65)) at the age of four months, were non‐inferior. Throughout the study, anthropometric z‐scores tracked closely against the WHO standards (within ±1 SD). In sum, a fourstage, age‐based infant formula system with nutritional compositions tailored to infants’ evolving needs, supports healthy growth consistent with WHO standards, for the first year of life