Decoding the HMO‒microbiome axis: bridging maternal milk to infant health outcomes

Human milk oligosaccharides (HMO) are unique glycans in breast milk that critically mediate interactions between the microbiome and infant health. This review synthesizes recent advances in understanding HMOs as key connectors of maternal and neonatal microbiomes with health outcomes. HMO composition, shaped by genetic factors (e.g., Secretor/Lewis status), lactation stage, maternal diet, and health, exhibits significant structural diversity. Critically, a bidirectional relationship exists between HMOs and the maternal microbiota: the maternal microbiome influences HMO biosynthesis, while HMOs selectively shape the microbial community within breast milk. In neonates, indigestible HMOs function as prebiotics, driving the assembly of a beneficial gut microbiota dominated by <i>Bifidobacterium</i>. This HMO-guided microbial establishment is fundamental to infant health, conferring protection against pathogenic infections (respiratory, gastrointestinal, and urinary), reducing the risk of necrotizing enterocolitis and allergies, and promoting healthy weight regulation, neurodevelopment, and bone mineralization. The modulation of host‒microbe interactions by HMOs underpins these systemic benefits, highlighting their central role as microbial and immunological regulators. Understanding the HMO-microbiome axis provides a holistic framework for elucidating how breast milk components foster infant development and disease resilience.