Human Milk Oligosaccharide Profiles over 12 Months of Lactation: The Ulm SPATZ Health Study

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.

Presence and Levels of Galactosyllactoses and Other Oligosaccharides in Human Milk and Their Variation during Lactation and According to Maternal Phenotype

“…In addition to maternal genetic predisposition linked to the expression pattern of Se and Le blood group genes, total amounts of HMOS also varied according to lactation stage. In line with others (e.g., [ 3 , 4 , 5 , 39 , 40 ]), we showed that the nTPA of selected HMOS dropped sharply to about half in the first 4 months and thereafter remained largely stable until the end of the first year postpartum. Our group recently showed similar results in a large number of samples ( n = 1203) from a birth cohort study conducted in South Germany [ 40 ].…”

“…In line with others (e.g., [ 3 , 4 , 5 , 39 , 40 ]), we showed that the nTPA of selected HMOS dropped sharply to about half in the first 4 months and thereafter remained largely stable until the end of the first year postpartum. Our group recently showed similar results in a large number of samples ( n = 1203) from a birth cohort study conducted in South Germany [ 40 ]. In that study, we found that—in line with the decrease in total HMOS amounts—absolute concentrations of most individual HMOS decreased from 6 weeks to 6 months and 12 months postpartum.…”

“…The added value of expressing the changes in individual HMOS as relative values is that these data are not obscured by the changes in the total amount of oligosaccharides present in HM. For example, it has been shown previously that absolute concentrations of 2 -FL and LNnT are continuously decreasing over the first months postpartum [4,16,38,40], whereas we show here that relative levels of these HMOS are very stable during this period (Figures 1-3). In line with the increasing trends in absolute levels of 3-FL, 3 -SL and DFL over the first 6 to 12 months postpartum observed by Siziba et al [40], we found increased relative levels of these HMOS (Figures 1-3).…”

Dynamic Changes in Human Milk Oligosaccharides in Chinese Population: A Systematic Review and Meta-Analysis

“…DSLNT is another major acidic HMO. In several previous studies, the level of DSLNT declined from colostrum to transitional milk to mature milk, but the longitudinal changes were not significant [ 37 , 38 ]. Conversely, unlike the findings reported, we found that the concentration of DSLNT in the 61–120 day stage rose dramatically to at least 1.5 times that at preceding stages.…”

An Expert Panel Statement on the Beneficial Effects of Human Milk Oligosaccharides (HMOs) in Early Life and Potential Utility of HMO-Supplemented Infant Formula in Cow’s Milk Protein Allergy

“… 18 Hence, whether the HMO supplementation ultimately improves infant formula milk in a way that mimics the documented benefits of human milk remain to be further investigated. 42 , 44 …”