Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. Interindividual variation is largely driven by fucosyltransferase (FUT2 and FUT3) polymorphisms resulting in 4 distinct milk groups. Little is known regarding whether maternal physiological status contributes to HMO variability. We characterized the trajectories of 20 major HMOs and explored whether maternal pre-pregnancy body mass index (ppBMI), mode of delivery, or parity may affect milk HMO composition. Using longitudinal breastmilk samples from healthy mothers (n = 290) across 7 European countries, we characterized HMO composion and employed mixed linear models to explore associations of maternal characteristics with individual HMOs. We observed HMO-specific temporal trajectories and milk group dependencies. We observed relatively small but significant differences in HMO concentrations based on maternal ppBMI, mode of delivery and parity. Our findings suggest that HMO composition to be regulated time-dependently by an enzyme as well as substrate availability and that ppBMI, mode of delivery, and parity may influence maternal physiology to affect glycosylation marginally within the initital period of lactation. Our observational study is the largest European standardized and longitudinal (up to 4 months) milk collection study assessing HMO concentrations and basic maternal characteristics. Time of lactation and milk groups had the biggest impact on HMO variation. Future studies need to elucidate these observations and assess the physiological significance for the breastfed infant.

Breastfed infants tend to be less prone to infections and may have improved cognitive benefits compared to formula-fed infants. Human milk oligosaccharides (HMO) are the third most abundant component of human milk, but are absent from formulae. They may be partially responsible for the benefits of breastfeeding. In this cross-sectional observational study, the HMO composition of milk from Chinese mothers was studied to determine the impact of stage of lactation, mode of delivery and geographical location. The content of 10 HMO was measured by HPLC in 446 milk samples from mothers living in three different cities in China. Around 21% of the samples contained levels of 2′-fucosyllactose (2′-FL) below the limit of quantification, which is similar to the frequency of fucosyltransferase-2 non-secretors in other populations, but 2′-FL was detected in all samples. Levels of most of the HMO studied decreased during the course of lactation, but the level of 3-fucosyllactose increased. Levels of 2′-FL and 3-fucosyllactose seem to be strongly correlated, suggesting some sort of mechanism for co-regulation. Levels of 6′-sialyllactose were higher than those of 3′-sialyllactose at early stages of lactation, but beyond 2–4 months, 3′-sialyllactose was predominant. Neither mode of delivery nor geographical location had any impact on HMO composition.

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Human milk oligosaccharides (HMOs) are a major component of human milk, and play an important role in protecting the infant from infections. Preterm infants are particularly vulnerable, but have improved outcomes if fed with human milk. This study aimed to determine if the HMO composition of preterm milk differed from that of term milk at equivalent stage of lactation and equivalent postmenstrual age. In all, 22 HMOs were analyzed in 500 samples of milk from 25 mothers breastfeeding very preterm infants (< 32 weeks of gestational age, < 1500 g of birthweight) and 28 mothers breastfeeding term infants. The concentrations of most HMOs were comparable at equivalent postpartum age. However, HMOs containing α-1,2-linked fucose were reduced in concentration in preterm milk during the first month of lactation. The concentrations of a number of sialylated oligosaccharides were also different in preterm milk, in particular 3′-sialyllactose concentrations were elevated. At equivalent postmenstrual age, the concentrations of a number of HMOs were significantly different in preterm compared to term milk. The largest differences manifest around 40 weeks of postmenstrual age, when the milk of term infants contains the highest concentrations of HMOs. The observed differences warrant further investigation in view of their potential clinical impact.

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Rationale: Human milk oligosaccharides (HMOs) vary among mothers and genetic factors contribute to this variability. We assessed changes in HMO concentrations during the first year of lactation and the relationship with FUT2 Secretor group and FUT3 Lewis group defining genetic polymorphisms. Methods: Milk samples were collected from lactating mothers participating in the LIFE Child cohort in Leipzig, Germany. The concentrations of 24 HMOs in milk samples collected at 3 months (N = 156), 6 months (N = 122), and 12 months (N = 28) were measured using liquid chromatography. Concentrations of HMOs were compared at all time-points and were tested for their associations with FUT2 and FUT3 genetic variations by sPLS regression. Results: FUT2 SNP rs601338 was found to predominantly define the Secretor status Se-: 11.8% and it was highly correlated with 2 ′-fucosyllactose (2 ′ FL, p < 0.001) and lacto-N-fucosylpentaose-I (LNFP-I, p < 0.001). FUT3 SNPs rs28362459 and rs812936 were found to define Lewis status (Le-: 5.9%) and correlated with lacto-N-fucosylpentaose-II (LNFP-II, p < 0.001). A polygenic score predicted the abundance of 2 ′ FL levels within Secretors' milk (adj. R 2 = 0.58, p < 0.001). Mean concentrations of most of the individual HMOs, as well as the sums of the measured HMOs, the fucosylated HMOs, and the neutral HMOs were lower at 6 and 12 months compared to 3 months (p < 0.001). Conclusions: Secretor and Lewis status defined by specific FUT2 and FUT3 SNPs are confirmed to be good proxies for specific individual HMOs and milk group variabilities. The polygenic score developed here is an opportunity for clinicians to predict 2 ′ FL levels in milk of future mothers. These results show opportunities to strengthen our Lefebvre et al. HMO and Genetic Determinants understanding of factors controlling FUT2 and FUT3 functionality, the temporal changes and variability of HMO composition during lactation and eventually their significance for infant development.