α2,6-linked sialylated oligosaccharides riched in goat milk alleviate food allergy by regulating the gut flora and mucin O-glycosylation.

The nutritious goat milk has low allergenicity. Oligosaccharides represent one of the crucial functional constituents in goat milk, which are structurally similar to human milk oligosaccharides (HMOs). Currently, the anti-allergic activity of GMOs has not been reported. In this study, GMOs were efficiently separated into neutral (NGMOs) and sialylated (SGMOs) fractions, following by qualitative and quantitative analysis at the isomer level using online LC-MS/MS. Fifteen NGMOs and 28 SGMOs were detected in goat milk, with 10 SGMOs reported for the first time. Distinctly, α2,6-linked SGMOs were 3.9 times more abundant in goat milk than in bovine milk, with the total relative content of 6'SL, 3'SLN and 6'NGL in SGMOs approach to 60%, which is more similar to HMOs. Orally administering GMOs, especially α2,6-linked sialylated oligosaccharides, significantly alleviated food allergy in ovalbumin-induced BALB/c mice. SGMOs restored the balance of Lachnospiraceae, Erysipelotrichaceae, and Bacteroidaceae, reconstructed the intestinal mucosal barrier, especially restored the levels of fucosylation, sialylation, and sulfation of mucin O-glycans, increased the expression of four core type 2 O-glycans (F1H2N2, F2H2N2, S1F2H2N2, and A1F1H2N2) significantly. This is the first comprehensive study of the anti-allergic activity of GMOs, and the results lay the foundation for the development of GMOs-based natural anti-allergic components.