Breast Milk Oligosaccharides Contain Immunomodulatory Glucuronic Acid and LacdiNAc

• Published in: Molecular & Cellular Proteomics
• Main Authors: Jin, Chunsheng, Lundstrøm, Jon, Korhonen, Emma, Luis, Ana S., Bojar, Daniel
• Format: Text
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 2023
• Subjects: Research; Beluga; Beluga whale; Beluga*
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10509713/; https://doi.org/10.1016/j.mcpro.2023.100635

Breast milk is abundant with functionalized milk oligosaccharides (MOs) to nourish and protect the neonate. Yet we lack a comprehensive understanding of the repertoire and evolution of MOs across Mammalia. We report ∼400 MO-species associations (>100 novel structures) from milk glycomics of nine mostly understudied species: alpaca, beluga whale, black rhinoceros, bottlenose dolphin, impala, L'Hoest's monkey, pygmy hippopotamus, domestic sheep, and striped dolphin. This revealed the hitherto unknown existence of the LacdiNAc motif (GalNAcβ1-4GlcNAc) in MOs of all species except alpaca, sheep, and striped dolphin, indicating the widespread occurrence of this potentially antimicrobial motif in MOs. We also characterize glucuronic acid-containing MOs in the milk of impala, dolphins, sheep, and rhinoceros, previously only reported in cows. We demonstrate that these GlcA-MOs exhibit potent immunomodulatory effects. Our study extends the number of known MOs by >15%. Combined with >1900 curated MO-species associations, we characterize MO motif distributions, presenting an exhaustive overview of MO biodiversity.