Nutrition in the early years of life plays a fundamental role in newborn growth, immune maturation, metabolic regulation, endocrine signaling, and neurological development, specifically through its interaction with the developing gut microbiota. Breast milk is the biological gold standard for infant nutrition; however, when breastfeeding is not possible, the development of formulations supplemented with bioactive substances can improve functional outcomes in comparison to standard milk formula. This narrative review discusses current evidence on formulas enriched with prebiotics, probiotics, postbiotics, synbiotics, human milk oligosaccharides, and other bioactive molecules. The review focuses on gut microbiota modulation, gastrointestinal function, growth and nutritional adequacy, immune development, infection-related outcomes, safety and tolerability, endocrine signaling, intestinal stem-cell regulation, obesity-related metabolic pathways, and emerging gut-brain axis interactions. Overall, available data indicate that bioactive-supplemented formulas are generally safe, well tolerated, and able to support normal growth, including in selected infants with specific clinical conditions. The most consistent effects are observed in the gastrointestinal tract, where supplementation promotes a more bifidogenic microbial profile, improves stool characteristics, supports intestinal barrier function, and influences microbial metabolic activity. By contrast, evidence regarding systemic immune effects, endocrine modulation, obesity prevention, and neurodevelopmental outcomes remains promising but heterogeneous and is still largely derived from preliminary human studies and experimental models. Therefore, these formulas may be considered a useful option when breastfeeding is not feasible, provided that their use is clinically appropriate and evidence based. Further studies are needed to clarify their long-term functional and clinical implications.
