Seal milk oligosaccharides rival human milk complexity and exhibit functional dynamics during lactation

Milk oligosaccharides are crucial for neonatal development and health in mammals. Yet most milk research focuses on humans, or on domesticated mammals that are poor in milk oligosaccharide complexity. Here, we perform an exhaustive mass spectrometry-driven structural characterization of milk oligosaccharides in a wild mammal, female Atlantic grey seals (Halichoerus grypus), throughout their lactation period. Characterizing and quantifying 332 milk oligosaccharides, including 166 unreported structures, we reveal seals to rival human milk in complexity. We report seal free oligosaccharides to reach up to 28 monosaccharides in size. Paired glycomics and metabolomics time course analysis establishes a concerted regulatory process reshaping the seal milk glycome throughout lactation, similar to human milk. Functional analysis of the structures we here characterized reveals anti-biofilm effects and immunomodulatory functions of seal milk oligosaccharides. Our findings challenge long-held assumptions about milk complexity of non-human mammals and enable insights into the functional relevance of complex carbohydrates in milk.