Beyond nutrition: a comprehensive review of the multifaceted benefits of HMOs and Bifidobacterium-based synbiotics during early life.

Early in life, gut, immunity, growth, and brain development occur rapidly and vary considerably. Growing evidence suggests that probiotics, prebiotics, and synbiotics effectively support host health during early life. Bifidobacterium is the dominant microbiota in the infant gut, while human milk oligosaccharides (HMOs) function as natural prebiotics in breast milk. Synbiotics combining HMOs and Bifidobacterium have been proposed. This review systematically elucidates the interaction between HMOs and Bifidobacteria, providing theoretical support for synbiotics based on both. The mechanisms by which Bifidobacteria utilize HMOs are classified as "exogenous degradation" and "endogenous degradation". Furthermore, this review summarizes the preclinical and clinical evidence regarding HMOs and Bifidobacterium-based synbiotics in promoting host health and preventing early-life diseases. Mechanistically, synbiotics primarily regulate host gut health and immune function through direct effects. Additionally, synbiotics exert their effects on non-gut health mainly through indirect mechanisms, manifested in the production of beneficial metabolites (e.g., short-chain fatty acids (SCFAs), indole derivatives, gamma-aminobutyric acid (GABA), sialic acid, and 5-hydroxytryptamine (5-HT)).