NEC-Associated Bronchopulmonary Dysplasia and the Gut–Lung Axis in Preterm Infants

Prevailing evidence underscores the critical influence of infant gut microbiota on systemic immune responses and intestinal health. The role of functional programming of effector immune cells at extra-intestinal mucosal sites is increasing in interest. Common connections between development of gut and lung microbiomes and reciprocal signaling between the two organ systems has reinforced the concept of a "gut-lung axis." Narrative review of existing literature evaluating mechanistic evidence linking microbial dysbiosis and necrotizing enterocolitis (NEC) to development of preterm acute lung injury and subsequent progression to chronic lung disease or bronchopulmonary dysplasia (BPD). Evidence across animal and human studies indicates that gut-derived microbial ligands and metabolites are foundational in programming respiratory immunity. Conversely, primary pulmonary insults appear to trigger reciprocal shifts in gut microbiome function. This bidirectional signaling likely drives the clinical association between NEC-associated systemic inflammation and the subsequent increased risk of BPD. By focusing on mediators involved in this gut-lung crosstalk, we seek to highlight avenues such as microbiome modulation or targeted anti-inflammatory signaling to prevent or reduce the severity of two of the major morbidities of prematurity. · Gut dysbiosis drives systemic inflammation and mediates pro-inflammatory responses in the lungs.. · The communication between gut and lungs is mediated by microbiome, metabolites and immune cells.. · Modulating the gut microbiome presents a promising strategy for prevention of BPD in preterm infants.