Probiotic modulation of gut microbiota in preterm infants: a narrative review of clinical evidence, mechanisms, and translational gaps

Preterm infants are at a heightened risk for gut dysbiosis, a condition characterized by reduced microbial diversity, delayed colonization by beneficial commensals such as Bifidobacterium , and overgrowth of opportunistic pathogens. This disrupted microbial ecosystem is intricately linked to the pathogenesis of life-threatening conditions, including necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and feeding intolerance, and is also implicated in long-term neurodevelopmental and respiratory outcomes. Probiotic supplementation has emerged as a prominent strategy to shift the microbiota toward a more eubiotic-like composition and mitigate these risks. This narrative review synthesizes evidence from a wide range of randomized controlled trials, observational studies, systematic reviews, and meta-analyses to evaluate the clinical efficacy and microbiological impact of probiotics in preterm populations. The evidence indicates that probiotic interventions, particularly specific multi-strain formulations containing well-defined Lactobacillus and Bifidobacterium strains, are associated with significant reductions in the incidence of severe NEC (risk ratio 0.38–0.57) and all-cause mortality (risk ratio 0.69). However, their effect on preventing LOS and reducing colonization by multidrug-resistant organisms is less consistent. Probiotics consistently enhance the intestinal abundance of beneficial bacteria, modulate metabolic profiles, and reduce markers of intestinal inflammation. However, effects are strain-specific and cannot be extrapolated across products; future trials should report full strain identity, dose, viability, and product composition. Emerging evidence also suggests a potential role for probiotics in influencing immune cell development and the gut-brain axis, with implications for neurodevelopment and seizure prevention, though these findings are preliminary. This review also addresses critical challenges, including the considerable heterogeneity in study designs, probiotic strains, and clinical protocols, safety concerns in extremely low-birth-weight infants, and the methodological issues related to product quality and taxonomic identification. We conclude that multi-strain probiotics reduce severe NEC and all-cause mortality, but evidence for LOS is inconsistent and neurodevelopmental benefit remains unproven. Routine universal use is therefore not justified; translation requires product-specific trials and regulatory-grade quality control.