Gastrointestinal Journey of Human Milk Oligosaccharides: From Breastfeeding Origins to Functional Roles in Adults.

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk and play crucial roles in shaping the gut microbiome and promoting infant health. Although their functions during infancy are well established, emerging evidence suggests that HMOs exert region-specific effects throughout the gastrointestinal tract, extending their benefits beyond early life. This review summarizes current findings on HMO activity in the oral cavity, stomach, small intestine, and large intestine, focusing on their microbiota-modulating, barrier-enhancing, and immunoregulatory effects. In the oral cavity, HMOs inhibit pathogen adhesion and biofilm formation, maintaining oral homeostasis. In the stomach, fucosylated and sialylated HMOs act as soluble decoy receptors, preventing Helicobacter pylori infection. In the small intestine, HMOs strengthen epithelial integrity, regulate inflammation, and promote nutrient absorption. In the large intestine, they serve as selective prebiotics for beneficial microbes, enhancing short-chain fatty acid production and improving barrier function. Although preclinical and clinical studies demonstrate their safety and efficacy, further research is required to elucidate their mechanisms in adults. Overall, HMOs represent multifunctional bioactive glycans with promising applications for gastrointestinal health across all ages.