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Human milk and infant formulae: Peptide differences and the opportunity to address the functional gap

ABSTRACT: Bovine-derived formula milk (FM) is a common substitute to human milk (HM), but lacks key functional benefits associated with HM. Accordingly, there have been significant efforts to humanise FM. Recent research has demonstrated that HM-derived peptides convey an array of beneficial bioactivities. Given that peptides serve as important signalling molecules offering high specificity and potency, they represent a prime opportunity to humanise FM. To further understand how HM-derived peptides contribute to infant health, we used peptidomics and bioinformatics to compare the peptide profile of HM to commercially available FM. We found clear and substantial differences between HM and FM in terms of peptide physicochemical properties, protein coverage and abundance. We additionally identified 618 peptides specific to HM that represent an important untapped source to be explored for novel bioactivities. While further study is required, our findings highlight the potential of a peptide-based approach to address the functional gap in FM. Graphical abstract Image 1 Highlights • The peptide component of human milk is under explored compared to formula milk• Marked differences in peptide profiles of human milk and formula milk were noted in Liquid Chromatography with tandem mass spectrometry data• We observed a set of human milk-specific peptides with reported bioactivities with no homologous peptides present formula milk• A larger set of human milk-specific peptides were identified with undetermined bioactivity• Further research is needed to elucidate novel human milk-specific bioactivities

SUBMITTER: Lopez C

PROVIDER: S-EPMC7782925 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Project description:BackgroundA limited number of nondigestible oligosaccharides are available for use in infant formula. This study evaluated growth and safety in infants fed formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS). This mixture, which was generated from whey permeate, contains galactooligosaccharides and other oligosaccharides from bovine milk, such as 3'- and 6'-sialyllactose. We hypothesized that growth in infants fed BMOS-supplemented formula would be noninferior to that in infants fed standard formula.MethodsHealthy term infants ≤14 days old were randomly assigned to standard formula (control; n = 84); standard formula with BMOS (IF-BMOS; n = 99); or standard formula with BMOS and probiotics (Bifidobacterium longum, Lactobacillus rhamnosus) (IF-BMOS + Pro; n = 98). A breastfed reference group was also enrolled (n = 30). The primary outcome was mean weight gain/day from enrollment to age 4 months (noninferiority margin: -3.0 g/day).Results189 (67.3%) formula-fed infants were included in the primary analysis. Mean differences in weight gain between the control and IF-BMOS and IF-BMOS + Pro groups were <1 g/day, with 97.5% confidence intervals above -3.0 g/day, indicating noninferior weight gain in the BMOS formula groups. Compared with control, infants in the BMOS groups had more frequent (p < 0.0001) and less hard (p = 0.0003) stools. No significant differences were observed between the control and BMOS groups in caregivers' reports of flatulence, vomiting, spitting up, crying, fussing, and colic. When based on clinical evaluation by the investigator, the incidence of colic was higher (p = 0.01) in IF-BMOS than in control; the incidence of investigator-diagnosed colic was not significantly different in control and IF-BMOS + Pro (p = 0.15). Stool bifidobacteria and lactobacilli counts were higher with IF-BMOS + Pro compared with control (p < 0.05), whereas Clostridia counts were lower (p < 0.05) in both BMOS groups compared with control.ConclusionsInfant formula containing BMOS either with or without probiotics provides adequate nutrition for normal growth in healthy term infants. Further studies are needed to fully explore the digestive tolerance of BMOS formula.Trial registrationClinicalTrials.gov NCT01886898 . Registered 24 June 2013.

Project description:BackgroundBreastfed infants have lower disease risk compared to formula-fed infants, however, the mechanisms behind this protection are unknown. Human milk has a complex lipidome which may have many critical roles in health and disease risk. However, human milk lipidomics is challenging, and research is still required to fully understand the lipidome and to interpret and translate findings. This study aimed to address key human milk lipidome knowledge gaps and discuss possible implications for early life health.MethodsHuman milk samples from two birth cohorts, the Barwon Infant Study (n = 312) and University of Western Australia birth cohort (n = 342), were analysed using four liquid chromatography-mass spectrometry (LC-MS) methods (lipidome, triacylglycerol, total fatty acid, alkylglycerol). Bovine, goat, and soy-based infant formula, and bovine and goat milk were analysed for comparison. Composition was explored as concentrations, relative abundance, and infant lipid intake. Statistical analyses included principal component analysis, mixed effects modelling, and correlation, with false discovery rate correction, to explore human milk lipidome longitudinal trends and inter and intra-individual variation, differences between sample types, lipid intakes, and correlations between infant plasma and human milk lipids.ResultsLipidomics analysis identified 979 lipids. The human milk lipidome was distinct from that of infant formula and animal milk. Ether lipids were of particular interest, as they were significantly higher, in concentration and relative abundance, in human milk than in formula and animal milk, if present in the latter samples at all. Many ether lipids were highest in colostrum, and some changed significantly through lactation. Significant correlations were identified between human milk and infant circulating lipids (40% of which were ether lipids), and specific ether lipid intake by exclusively breastfed infants was 200-fold higher than that of an exclusively formula-fed infant.ConclusionThere are marked differences between the lipidomes of human milk, infant formula, and animal milk, with notable distinctions between ether lipids that are reflected in the infant plasma lipidome. These findings have potential implications for early life health, and may reveal why breast and formula-fed infants are not afforded the same protections. Comprehensive lipidomics studies with outcomes are required to understand the impacts on infant health and tailor translation.

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Human milk and infant formulae: Peptide differences and the opportunity to address the functional gap

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