A practical overview on biotics in infant formulas: Bridging human milk biology, clinical evidence and market dynamics

Early-life nutrition plays a crucial role in the development of gut microbiota, immune system maturation, intestinal function, and gut-brain axis signaling. Human breast milk is the gold standard for infant nutrition due to its dynamic composition and content of bioactive components, including human milk oligosaccharides and milkassociated microbiota, which support gut colonization and immune modulation. When breastfeeding is not possible or insufficient, infant formulas are used. Although nutritionally adequate and safe, they do not reproduce the biological complexity of human milk. To reduce this gap, infant formulas are increasingly supplemented with biotics, such as prebiotics, probiotics, synbiotics, postbiotics, and synthetic HMO analogues. This review aims to deepen the current evidence on the safety and clinical effects of biotics-enriched infant formulas in infants. Available studies indicate a good safety profile and normal growth patterns. Modest effects on stool consistency and frequency have been observed, mainly with galacto-oligosaccharides and fructooligosaccharides, while evidence supporting other biotic combinations remains limited and heterogeneous. Despite increasing market adoption, robust clinical evidence supporting routine use is still insufficient. Further well-designed studies are needed to identify effective biotic combinations and evaluate their long-term health effects.