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Human milk oligosaccharides (HMOs) are a structurally diverse group of complex, unconjugated glycans that constitute the third most abundant solid component of human breast milk, following lactose and lipids (Wiciński et al., 2020). Unlike other milk components, HMOs are not digested by the infant's enzymes but instead reach the distal gut, where they serve as selective prebiotics for beneficial bacteria, particularly Bifidobacterium species (Rousseaux et al., 2021). Beyond their role in microbiome modulation, HMOs function as soluble decoy receptors that mimic host cell surface glycans, preventing the adhesion of various viral, bacterial, and protozoan pathogens to the intestinal mucosa (Wikipedia, 2024). They also exert direct immunomodulatory effects by interacting with immune cell receptors, such as lectins and Toll-like receptors, and by strengthening the intestinal epithelial barrier (Frontiers in Immunology, 2021). Clinically, specific HMOs like 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) are increasingly used as supplements in infant formula and are being investigated for therapeutic applications in adults for conditions such as irritable bowel syndrome and allergy prevention (Frontiers in Nutrition, 2024). While not traditional protein targets, HMOs represent a significant class of bioactive molecules with broad therapeutic potential in neonatal and adult health.
HMOs function through multiple mechanisms: they act as prebiotics by selectively promoting the growth of beneficial gut bacteria (e.g., Bifidobacterium); they serve as soluble decoy receptors that bind to pathogens, preventing their attachment to host cell surface glycans; they directly modulate the immune system by interacting with receptors like lectins and Toll-like receptors; and they enhance the intestinal barrier by promoting tight junction protein expression and mucus production (Wiciński et al., 2020; Rousseaux et al., 2021).
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