Background: Neonatologists face a significant clinical challenge in balancing the life-saving effects of broad-spectrum antibiotics with an infant’s ability to develop long-term vaccine-induced immunity. During the critical neonatal window, the gut microbiota acts as an essential endogenous adjuvant that promotes immune maturation through Toll-like receptor signaling and the production of microbial metabolites such as short-chain fatty acids. Methods: This narrative review was based on a comprehensive search of the PubMed and Google Scholar databases for studies published between 2014 and 2025. The search focused on the relationships between neonatal antibiotic exposure, gut microbiome development, and vaccine-induced immune responses in infants. Results: Early-life antibiotic exposure disrupts immune maturation by causing a marked reduction in commensal bacteria, particularly Bifidobacterium and Bacteroides. Clinical and epidemiological evidence indicates that this antibiotic-driven dysbiosis leads to significantly lower antibody titers following routine vaccinations, including PCV13, Hib, and DTaP, with measurable effects persisting up to 15 months of age. While antibiotics may paradoxically enhance oral rotavirus vaccine responses in resource-constrained settings by reducing environmental enteric dysfunction, an undisturbed native microbiota remains the optimal foundation for robust immunological memory. Conclusions: These findings highlight the necessity of improving antibiotic stewardship and exploring microbiota-restoring interventions, such as targeted probiotics, to optimize infant vaccination schedules and protect long-term immune health. Empirical antibiotic treatment should be promptly terminated once sepsis has been clinically excluded to preserve the gut–immune axis.
Babik et al. (Thu,) studied this question.