Dataset Information

Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes - A Randomized Controlled Trial.

ABSTRACT: In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age.The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk.In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of age were randomized to be fed experimental formula (EF, n = 80) with reduced energy and protein and supplemented with a bovine MFGM concentrate, or standard formula (SF, n = 80) until 6 months of age. A breast-fed reference (BFR, n = 80) group was also recruited. The oral microbiota was analyzed at 4 (n = 124) and 12 (n = 166) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA database of oral bacteria.Species richness in the oral samples did not differ between the EF and SF groups, but partial least square modeling identified a few taxa that were significantly associated with being in either group, e.g. lower level of Moraxella catarrhalis in the EF group. Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups.Supplementation of infant formula with MFGM yielded moderate effects on the oral microbiome. Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group.

SUBMITTER: Timby N

PROVIDER: S-EPMC5242539 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes - A Randomized Controlled Trial.

Timby Niklas N Domellöf Magnus M Holgerson Pernilla Lif PL West Christina E CE Lönnerdal Bo B Hernell Olle O Johansson Ingegerd I

PloS one 20170118 1

<h4>Background</h4>In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age.<h4>Objectives</h4>The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk.<h4>Methods</h4>In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of ...[more]

PMID: 28099499

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Project description:BackgroundProteins and lipids of milk fat globule membrane (MFGM) and probiotics are immunomodulatory. We hypothesized that Lactobacillus paracasei ssp. paracasei strain F19 (F19) would augment vaccine antibody and T helper 1 type immune responses whereas MFGM would produce an immune response closer to that of breastfed (BF) infants.ObjectiveTo compare the effects of supplementing formula with F19 or bovine MFGM on serum cytokine and vaccine responses of formula-fed (FF) and BF infants.DesignFF infants were randomized to formula with F19 (n = 195) or MFGM (n = 192), or standard formula (SF) (n = 194) from age 21±7 days until 4 months. A BF group served as reference (n = 208). We analyzed seven cytokines (n = 398) in serum at age 4 months using magnetic bead-based multiplex technology. Using ELISA, we analyzed anti-diphtheria IgG (n = 258) and anti-poliovirus IgG (n = 309) concentrations in serum before and after the second and third immunization, respectively.ResultsCompared with SF, the F19 group had greater IL-2 and lower IFN-γ concentrations (p<0.05, average effect size 0.14 and 0.39). Compared with BF, the F19 group had greater IL-2, IL-4 and IL-17A concentrations (p<0.05, average effect size 0.42, 0.34 and 0.26, respectively). The MFGM group had lower IL-2 and IL-17A concentrations compared with SF (p<0.05, average effect size 0.34 and 0.31). Cytokine concentrations were comparable among the MFGM and BF groups. Vaccine responses were comparable among the formula groups.ConclusionsContrary to previous studies F19 increased IL-2 and lowered IFN-γ production, suggesting that the response to probiotics differs across populations. The cytokine profile of the MFGM group approached that of BF infants, and may be associated with the previous finding that infectious outcomes for the MFGM group in this cohort were closer to those of BF infants, as opposed to the SF group. These immunomodulatory effects support future clinical evaluation of infant formula with F19 or MFGM.

Project description:IntroductionMilk fat globule membrane (MFGM) is a complex lipid-protein structure in mammalian milk and human milk that is largely absent from breastmilk substitutes. The objective of this trial is to investigate whether providing infant formula enriched with MFGM versus standard infant formula improves cognitive development at 12 months of age in exclusively formula-fed full-term infants.Methods and analysisThis is a randomised, controlled, clinician-blinded, researcher-blinded and participant-blinded trial of two parallel formula-fed groups and a breastfed reference group that were recruited in the suburban Adelaide (Australia) community by a single study centre (a medical research institute). Healthy, exclusively formula-fed, singleton, term-born infants under 8 weeks of age were randomised to either an MFGM-supplemented formula (intervention) or standard infant formula (control) from enrolment until 12 months of age. The reference group was not provided with formula. The primary outcome is the Cognitive Scale of the Bayley Scales of Infant Development, Fourth Edition (Bayley-IV) at 12 months. Secondary outcomes are the Bayley-IV Cognitive Scale at 24 months, other Bayley-IV domains (language, motor, emotional and behavioural development) at 12 and 24 months of age, infant attention at 4 and 9 months of age, parent-rated language at 12 and 24 months of age, parent-rated development at 6 and 18 months of age as well as growth, tolerance and safety of the study formula. To ensure at least 80% power to detect a 5-point difference in the mean Bayley-IV cognitive score, >200 infants were recruited in each group.Ethics and disseminationThe Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/19/WCHN/140). Caregivers gave written informed consent prior to enrolling in the trial. Findings of this study will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberACTRN12620000552987; Australian and New Zealand Clinical Trial Registry: anzctr.org.au.

Project description:Introduction: Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. BM, and the changes in the gut microbiota, but few also focus on intestinal inflammation. Methods: We conducted a cohort study of newborn infants during their first 3 months. In stool samples taken at 1 and 3 months (timepoints T1 and T3), we quantified calprotectin, IL-8 and ?1-antitrypsin by ELISA and we evaluated the expression of IL8 and IL1? genes by RT-qPCR. To determine the microbiota composition, the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs). Results: In total 15 BM and 10 BF infants were enrolled. In the BM group, we found calprotectin and ?1-antitrypsin levels were significantly elevated at T3 compared to T1; no differences were found between T1 and T3 in the BF group. A comparison between the BM and BF groups showed that calprotectin levels at T1 were lower in the BM than the BF group; this difference was not observed at T3. For IL-8 levels, we found no differences between groups. A gene expression analysis of the IL8 and IL1? genes showed that infants from the BF group at T1 have a significantly increased expression of these markers compared to the BM group. Gut microbiota analyses revealed that the phylum Bacteroidetes was higher in BM than BF, whereas Firmicutes were higher in BF. A redundancy analysis and ANOVA showed BM has a community structure statistically different to BF at T1 but not at T3. Compared to BF, BM at T1 showed a higher representation of Enterococcus, Streptococcus, Enterobacter, Lactococcus, and Propionibacterium. Conclusions: We found a basal state of inflammation in the infants' intestine based on inflammation markers. One month after birth, infants receiving BF exhibited higher levels of inflammation compared to BM.

Project description:BackgroundBovine milk-derived oligosaccharides (MOS) containing primarily galacto-oligosaccharides with inherent concentrations of sialylated oligosaccharides can be added to infant formula to enhance the oligosaccharide profile.ObjectiveTo investigate the effects of an MOS-supplemented infant formula on gut microbiota and intestinal immunity.MethodsIn a double-blind, randomized, controlled trial, healthy term formula-fed infants aged 21-26 d either received an intact protein cow milk-based formula (control group, CG, n = 112) or the same formula containing 7.2 g MOS/L (experimental group, EG, n = 114) until the age of 6 mo. Exclusively human milk-fed infants (HFI, n = 70) from an observational study served as the reference. Fecal samples collected at baseline, and the ages of 2.5 and 4 mo were assessed for microbiota (16S ribosomal RNA-based approaches), metabolites, and biomarkers of gut health and immune response.ResultsAged 2.5 and 4 mo, redundancy analysis (P = 0.002) and average phylogenetic distance (P < 0.05) showed that the overall microbiota composition in EG was different from CG and closer to that of HFI. Similarly, EG caesarean-born infants were different from CG caesarean- or vaginally born infants and approaching HFI vaginally born infants. Relative bifidobacteria abundance was higher in EG compared with CG (P < 0.05) approaching HFI. At the age of 4 mo, counts of Clostridioides difficile and Clostridium perfringens were ∼90% (P < 0.001) and ∼65% (P < 0.01) lower in EG compared with CG, respectively. Geometric LS mean (95% CI) fecal secretory IgA in EG was twice that of CG [70 (57, 85) compared with 34 (28, 42) mg/g, P < 0.001] and closer to HFI. Fecal oral polio vaccine-specific IgA was ∼50% higher in EG compared with CG (P = 0.065). Compared with CG, EG and HFI had lower fecal calcium excretion (by ∼30%, P < 0.005) and fecal pH (P < 0.001), and higher lactate concentration (P < 0.001).ConclusionsInfant formula with MOS shifts the gut microbiota and metabolic signature closer to that of HFI, has a strong bifidogenic effect, reduces fecal pathogens, and improves the intestinal immune response.

Project description:Human milk represents an optimal source of nutrition during infancy. Milk also serves as a vehicle for the transfer of growth factors, commensal microbes, and prebiotic compounds to the immature gastrointestinal tract. These immunomodulatory and prebiotic functions of milk are increasingly appreciated as critical factors in the development of the infant gut and its associated microbial community. Advances in infant formula composition have sought to recapitulate some of the prebiotic and immunomodulatory functions of milk through human milk oligosaccharide (HMO) fortification, with the aim of promoting healthy development both within the gastrointestinal tract and systemically. Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2'-fucosyllactose (2'-FL) on serum metabolite levels relative to breastfed infants. A prospective, randomized, double-blinded, controlled study of infant formulas (64.3 kcal/dL) fortified with varying levels of 2'-FL and galactooligosaccharides (GOS) was conducted [0.2 g/L 2'-FL + 2.2 g/L GOS; 1.0 g/L 2'-FL + 1.4 g/L GOS]. Healthy singleton infants age 0-5 days and with birth weight > 2490 g were enrolled (n = 201). Mothers chose to either exclusively formula-feed or breastfeed their infant from birth to 4 months of age. Blood samples were drawn from a subset of infants at 6 weeks of age (n = 35-40 per group). Plasma was evaluated by global metabolic profiling and compared to a breastfed reference group (HM) and a control formula (2.4 g/L GOS). Fortification of control infant formula with the HMO 2'-FL resulted in significant increases in serum metabolites derived from microbial activity in the gastrointestinal tract. Most notably, secondary bile acid production was broadly increased in a dose-dependent manner among infants receiving 2'-FL supplemented formula relative to the control formula. 2'-FL supplementation increased secondary bile acid production to levels associated with breastfeeding. Our data indicate that supplementation of infant formula with 2'-FL supports the production of secondary microbial metabolites at levels comparable to breastfed infants. Thus, dietary supplementation of HMO may have broad implications for the function of the gut microbiome in systemic metabolism. This trial was registered at with the U.S. National library of Medicine as NCT01808105.

Dataset Information

Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes - A Randomized Controlled Trial.

Publications

Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes - A Randomized Controlled Trial.

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