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. R2 = 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
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