Abstract
Background/Objectives: The gut microbiota (GM) is pivotal for immune regulation, metabolism, and neurodevelopment. Infants undergoing surgery for congenital gastrointestinal anomalies are especially prone to microbial imbalances, with a paucity of beneficial bacteria (e.g., Bifidobacteria and Bacteroides) and diminished short-chain fatty acid production. Dysbiosis has been associated with severe complications, including necrotizing enterocolitis, sepsis, and feeding intolerance. This narrative review aims to critically examine strategies for microbiota modulation in this high-risk cohort. Methods: An extensive literature analysis was performed to compare the evolution of GM in healthy neonates versus those requiring gastrointestinal surgery, synthetizing strategies to maintain eubiosis, such as early nutritional interventions-particularly the use of human milk-along with antibiotic management and supplementary treatments including probiotics, prebiotics, postbiotics, and lactoferrin. Emerging techniques in metagenomic and metabolomic analysis were also evaluated for their potential to elucidate microbial dynamics in these patients. Results: Neonates undergoing gastrointestinal surgery exhibit significant alterations in microbial communities, characterized by reduced levels of eubiotic bacteria and an overrepresentation of opportunistic pathogens. Early initiation of enteral feeding with human milk and careful antibiotic stewardship are linked to improved microbial balance. Adjunctive therapies, such as the administration of probiotics and lactoferrin, show potential in enhancing gut barrier function and immune modulation, although confirmation through larger-scale studies remains necessary. Conclusions: Modulating the GM emerges as a promising strategy to ameliorate outcome in neonates with congenital gastrointestinal surgical conditions. Future research should focus on the development of standardized therapeutic protocols and the execution of rigorous multicenter trials to validate the efficacy and safety of these interventions.