Maternal and Infant Factors Associated with Human Milk Oligosaccharides Concentrations According to Secretor and Lewis Phenotypes

Abstract

Human milk oligosaccharides (HMOs) are multifunctional carbohydrates naturally present in human milk that act as prebiotics, prevent pathogen binding and infections, modulate the immune system and may support brain development in infants. HMOs composition is very individualized and differences in HMOs concentrations may affect the infant’s health. HMOs variability can be partially explained by the activity of Secretor (Se) and Lewis (Le) genes in the mother, but non-genetic maternal factors may also be involved. In this cross-sectional, observational study, 78 single human milk samples ranging from 17 to 76 days postpartum (median: 32 days, IQR: 25–46 days) were collected from breastfeeding Brazilian women, analyzed for 16 representative HMOs by liquid chromatography coupled to mass spectrometry and associations between maternal and infant factors with HMOs concentrations were investigated. HMOs concentrations presented a high variability even in women with the same SeLe phenotype and associations with maternal allergic disease, time postpartum and with infant’s weight, weight gain and sex. Overall, we present unprecedented data on HMOs concentrations from breastfeeding Brazilian women and novel associations of maternal allergic disease and infant’s sex with HMOs concentrations. Differences in HMOs composition attributed to maternal SeLe phenotype do not impact infant growth, but higher concentrations of specific HMOs may protect against excessive weight gain.

Neutral Human Milk Oligosaccharides Are Associated with Multiple Fixed and Modifiable Maternal and Infant Characteristics

“…The frequency of the SeLe phenotypes vary ethnically [18,29,40]. In our cohort, the Secretor and Lewis phenotypes were determined by the concentration of 2 -FL and LNFP-II as previous studies have also done [17,24,35]. We found that 76.7% mothers were Se+Le+ phenotype, 17.2% were Se-Le+, 4.3% were Se+Le-, and just 2 (1.7%) were Se-Le-.…”

“…Those who presented α1,4-fucosylated HMOs were distributed as Lewis positive (Le+) group, others were classified as Lewis negative (Le-) group. As previous studies have done [17,24,35], we chose 2 -FL and LNFP-II as representative HMOs for α1,2and α1,4-fucosylated HMOs. 2 -FL and LNFP-II fell steeply in Se-and Le-group, respectively.…”

“…Beyond genetic factors, several studies reported that HMOs composition varied with lactation stage [11,15,17,[20][21][22][23][24][25][26]. However, most studies collected samples in a single time point or focused on first few weeks of lactation.…”

Modifications of Own Mothers’ Milk Fortification Protocol Affect Early Plasma IGF-I and Ghrelin Levels in Preterm Infants. A Randomized Clinical Trial

“…Another limitation is the fact that the mid-infrared milk analyzers cannot discriminate lactose from other non-digestible oligosaccharides. Previous studies reported a wide range of human milk oligosaccharide concentrations (12% to 30%), depending on gestational age, duration of breast feeding, ethnicity, maternal BMI, and other factors [29,[32][33][34][35]. For this reason, we calculated lactose concentration, referred to as estimated lactose, and the lactose-derived energy of OMM assuming that oligosaccharides constitute 20% of total carbohydrates in human milk.…”

“…, and lipid (g•kg −1 •d −1 ) intake were calculated including milk content and the amount of HMF as well as the parenterally administered macronutrients. Lactose intake was calculated from the total carbohydrates measured in OMM assuming a 20% of total carbohydrates as non-metabolized oligosaccharides [29][30][31][32][33][34][35]. Energy intake was calculated from the macronutrient concentrations by using the Atwater factors: 9 kcal/g for fat and 4 kcal/g for protein and estimated lactose.…”