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Human milk oligosaccharides (HMOs) are a structurally diverse group of complex, non-digestible carbohydrates that represent the third most abundant solid component of human breast milk, following lactose and lipids [1.2.1, 1.2.2]. They are not primarily used for energy but function as bioactive molecules that play critical roles in infant health and development [1.1.2, 1.2.4]. HMOs serve as prebiotics by selectively promoting the growth of beneficial gut bacteria, such as Bifidobacterium, and act as soluble decoy receptors that prevent the adhesion of pathogens to the intestinal epithelium [1.2.2, 1.3.3]. Additionally, they directly modulate the immune system by interacting with cell surface receptors and contribute to gut barrier maturation and neurodevelopment [1.1.2, 1.2.4]. Clinically, HMOs are associated with a reduced risk of necrotizing enterocolitis, gastrointestinal and respiratory infections, and allergic diseases [1.2.2, 1.3.2]. Specific HMOs, such as 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT), are now produced through industrial fermentation for use in infant formula and are being explored as novel immunotherapeutics for both infants and adults [1.1.3, 1.2.5].
HMOs function through multiple mechanisms: they act as prebiotics by selectively nourishing beneficial gut bacteria like Bifidobacterium; they serve as soluble decoy receptors that mimic host cell surface glycans to prevent pathogen adhesion; and they directly modulate immune cells by binding to receptors such as lectins, Siglecs, and Galectins [1.1.2, 1.2.2, 1.3.2].
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