Abstract

Human milk oligosaccharides (HMOs) have specific dose-dependent effects on child health outcomes. The HMO profile differs across mothers and is largely dependent on gene expression of specific transferase enzymes in the lactocytes. This study investigated the trajectories of absolute HMO concentrations at three time points during lactation, using a more accurate, robust, and extensively validated method for HMO quantification. We analyzed human milk sampled at 6 weeks (n = 682), 6 months (n = 448), and 12 months (n = 73) of lactation in a birth cohort study conducted in south Germany, using label-free targeted liquid chromatography mass spectrometry (LC-MS2). We assessed trajectories of HMO concentrations over time and used linear mixed models to explore the effect of secretor status and milk group on these trajectories. Generalized linear model-based analysis was used to examine associations between HMOs measured at 6 weeks of lactation and maternal characteristics. Results: Overall, 74%, 18%, 7%, and 1% of human milk samples were attributed to milk groups I, II, III, and IV, respectively. Most HMO concentrations declined over lactation, but some increased. Cross-sectionally, HMOs presented high variations within milk groups and secretor groups. The trajectories of HMO concentrations during lactation were largely attributed to the milk group and secretor status. None of the other maternal characteristics were associated with the HMO concentrations. The observed changes in the HMO concentrations at different time points during lactation and variations of HMOs between milk groups warrant further investigation of their potential impact on child health outcomes. These results will aid in the evaluation and determination of adequate nutrient intakes, as well as further (or future) investigation of the dose-dependent impact of these biological components on infant and child health outcomes.

Highlights

  • Human milk is considered the most suitable source of nutrition for infants

  • In subsequent group stratified analysis, we investigated the effect of maternal characteristics on the human milk oligosaccharides (HMOs) trajectories over 6 weeks and 6 months, up to 12 months of lactation within milk groups I and II using linear mixed models

  • Human milk samples were available for HMO analysis from 682, 448, and 73 lactating women at 6 weeks, 6 months, and 12 months, respectively (Table 1, Supplementary Tables S2 and S3)

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Summary

Introduction

Human milk is considered the most suitable source of nutrition for infants. In addition to other biological components, human milk oligosaccharides (HMOs) are the third largest solid component of human milk and constitute approximately 20% of the total carbohydrate content [1]. Compared to term milk (~17 g/L) and higher concentrations of HMOs have been reported in secretor milks (~18 g/L) [4]. In this case, secretor milk contains large amounts of specific HMO structures such as 2 -fucosyllactose (2 -FL) and lacto-N-fucopentaose I (LNFP I). Secretor milk contains large amounts of specific HMO structures such as 2 -fucosyllactose (2 -FL) and lacto-N-fucopentaose I (LNFP I) The presence of such structures and others is dependent on the expression of α1,2fucosyltransferase Se- and Fuc-TIII (α1–3 fucosyltransferase) enzymes [5,6]. Evidence suggests that HMOs function as prebiotics for the gut microbiota [20], possess antimicrobial activity [21], prevent pathogen binding and infections [22], modulate the immune system [23,24,25], and may be necessary for brain [26,27] and cognitive development [28]

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