Comparative analysis of milk and brain fatty acids reveals human-specific signatures in brain development.

Lipids constitute the majority of brain dry weight and play essential structural and signaling roles. During early life, their supply depends largely on breast milk, yet how milk composition aligns with brain fatty acids (FA) across species has not been systematically explored. We analyzed 837 milk samples from seven mammalian species and 194 brain samples from five species using LC-MS. We identified 81 FA in milk and 33 in brain, with 31 shared across both tissues. FA composition in milk and brain was strongly correlated, particularly in humans and macaques, with the strongest associations observed in the prefrontal cortex and during the first four weeks postpartum. Humans were uniquely enriched in very- and ultra-long-chain unsaturated FAs (≥24 carbons) in both milk and brain, suggesting a role in species-specific neurodevelopment. Infant formula clustered closer to bovids than to human milk, underscoring compositional differences of potential nutritional relevance. These findings reveal conserved and human-specific features of milk and brain FAs, highlight the importance of early milk supply for neurodevelopment, and provide evolutionary and translational insights into infant nutrition.