Abstract

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.

Highlights

  • Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period

  • Among the factors explaining part of the inter-individual HMO variability are the genetic variations affecting the activity of fucosyltransferase 2 and 3 (FUT2 and FUT3) enzymes that are encoded by the Secretor and Lewis gene respectively[4,16,20,21,22]

  • We explored the effect of delivery mode on the HMO concentrations over the first 4 months of lactation, adjusted for milk group, pre-pregnancy body mass index (ppBMI) and parity (Fig. 5)

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Summary

Introduction

Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. 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. While HMOs are well known for their role as a substrate in stimulating the growth of beneficial bacteria in the gastrointestinal tract of infants[5,6,7], emerging research data suggest that they may exert effects through multiple mechanisms in a structure function specific way. There is limited data available from only two studies to suggest a correlation between HMOs and maternal factors, such as body weight, body mass index (BMI), parity and age[23,24]

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