The microbial ecology established in the first weeks of life may be among the most consequential determinants of long-term health — and for the roughly 15 million preterm infants born globally each year, that ecology is profoundly disrupted from the start. Understanding precisely how and why carries implications not only for neonatal survival but for trajectories of neurological, pulmonary, and immune development that extend well into adulthood.
This comprehensive review in Clinical Microbiology Reviews synthesizes evidence on the distinctive microbial assembly pattern that characterizes preterm guts: low taxonomic diversity, marked depletion of Bifidobacterium species, and unchecked expansion of pathobionts within the Enterobacteriaceae family. The convergence of physiological immaturity, NICU environmental exposures, and repeated antibiotic courses creates what the authors frame as a dysbiotic ecosystem — one mechanistically linked to necrotizing enterocolitis (NEC), the devastating intestinal emergency that affects up to 10% of very-low-birthweight infants. Key pathways include aberrant Toll-like receptor 4 signaling, bile acid dysmetabolism, and systemic immune dysregulation. Critically, the review maps gut-organ axes connecting intestinal dysbiosis to brain, lung, retinal, and circulatory outcomes, extending the consequence of early microbial imbalance far beyond the gut itself.
What makes this review particularly relevant to the broader microbiome field is its translational scope. The authors evaluate interventions ranging from human milk feeding and antibiotic stewardship — still the highest-yield, most evidence-backed strategies — through probiotic and prebiotic supplementation, and into emerging territory: postbiotics, bacteriophage therapy, and fecal microbiota transplantation in neonates. The integration of multi-omics profiling, machine learning, and digital twin modeling signals a shift toward individualized, predictive microbiome management. However, a critical limitation persists: mechanistic insights from animal and observational studies have not yet translated into robust, large-scale randomized trials with standardized microbial endpoints. The antimicrobial resistance burden accumulating in preterm guts also represents an underappreciated systemic risk. This review is not incremental — it reframes neonatal dysbiosis as a systems-level problem demanding precision solutions.