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

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Venot, Eric | Dechaumet, Sylvain | Guillon, Blanche | Berdi, Mikaïl | Cholet, Sophie | Tajeddine, Ghita | Mutaner, Manon | Meirhaeghe, Aline | Heude, Barbara | Lauzon-Guillain, Blandine De | Thevenot, Etienne | Fenaille, François | Adel-Patient, And Karine

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International audience. Human Milk Oligosaccharides (HMO) are highly diverse and abundant components ofhuman breastmilk, known to play a key role in the development of the neonate microbiotaand 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 withpresence of lacto-N-fucopentaose II (LNFPII) and lacto-N-difucohexaose I (LNDFHI). Inthe present work, we aim to provide a comprehensive characterization of the global HMOcomposition depending on Se/Le status.Early BM samples collected within the EDEN mother-child cohort (n=317) were analysedusing 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 FUT2and FUT3 genes were available (n=62) for 220 out the 317 mothers.Comparison of HMO composition and FUT2/FUT3 genotypes showed that, except for onemother, 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 statuswas also associated with a particular HMO composition, far beyond the presence/absenceof 2’FL and LNFPI. Corresponding signature will then be related to EDEN children healthoutcome available up to their 5th birthday (ex: food allergy).

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