Impact of consumption of the human milk oligosaccharides 2-FL and LNnT on reduction of risk of allergic sensitisation

Human Milk Oligosaccharides (HMOs) have been proposed to be instrumental in building immune competence. To explore the role of HMOs in allergy prevention, twenty-one HMOs were quantified in breast milk samples and associated with sensitisation in infants. 2 '-fucosyllactose (2 '-FL) levels were positively associated with an increased risk of sensitisation, atopic dermatitis and recurrent skin rash. Interestingly, 2 '-FL levels, ranging from 1.35 to 1.95 g/L, were associated with a higher prevalence of non-allergic and non-sensitised infants. The role of 2 '-FL and lacto-N-neotetraose (LNnT) was further investigated in allergic sensitisation models in vivo. Oral administration of HMOs decreased allergic sensitisation. This was associated with gut microbiota and short-chain fatty acid (SCFA) production changes. Aligned with the clinical associations, the decreased sensitisation was not observed with lower and higher tested doses of the HMOs supporting a U-shape association between 2 '-FL and LNnT levels and allergic sensitisation risk reduction in humans and mice.Trial registration: ClinicalTrials.gov identifier: NCT02550236.