Influence of FUT2/FUT3 polymorphism on human breastmilk oligosaccharide composition in the EDEN mother-child cohort
Influence du polymorphisme FUT2/FUT3 sur la composition en oligosaccharides des laits maternels humains précoces de la cohorte mère-enfant EDEN
Résumé
Human Milk Oligosaccharides (HMO) are highly diverse and abundant components of
human breastmilk, known to play a key role in the development of the neonate microbiota
and immunity. HMO composition depends mainly on genetic polymorphisms of the mother,
notably on genes encoding FUT2 and FUT3 fucosyltransferase: as reported in the littera-
ture, FUT2 (secretor status, Se) induces synthesis of HMOs such as 2-fucosyllactose (2’FL)
and lacto-N-fucopentaose I (LNFPI), whereas FUT3 (Lewis status, Le) is associated with
presence of lacto-N-fucopentaose II (LNFPII) and lacto-N-difucohexaose I (LNDFHI). In
the present work, we aim to provide a comprehensive characterization of the global HMO
composition depending on Se/Le status.
Early BM samples collected within the EDEN mother-child cohort (n=317) were analysed
using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS, Q-
TOF instrument, Bruker) following a previously optimized protocol. A dedicated R annota-
tion workflow was developed, and led to the detection of 130 potential HMOs (among them,
2’FL, LNFPI, LNFPII and LNDFHI). Single Nucleotide Polymorphisms (SNP) in the FUT2
and FUT3 genes were available (n=62) for 220 out the 317 mothers.
Comparison of HMO composition and FUT2/FUT3 genotypes showed that, except for one
mother, 2’FL and LNFPI contents were associated with the FUT2 rs516246 SNP. In contrast,
FUT3 SNPs were not associated with specific HMO composition. Interestingly, the Se status
was also associated with a particular HMO composition, far beyond the presence/absence
of 2’FL and LNFPI. Corresponding signature will then be related to EDEN children health
outcome available up to their 5th birthday (ex: food allergy).
Origine | Fichiers produits par l'(les) auteur(s) |
---|