Abstract / Summary
Background/Objectives: Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity in preterm infants, and effective preventive strategies are lacking. This study investigated the protective effect of orally administered Limosilactobacillus reuteri DSM 17938 in a neonatal rat model of hyperoxia-induced lung injury. Methods: Newborn Sprague-Dawley rat pups were randomly allocated to normoxia control (NC), hyperoxia control (HC), and hyperoxia with probiotic supplementation (HP) groups. The HC and HP groups were exposed to 90% oxygen from postnatal day 1 to 14. L. reuteri DSM 17938 (3.3 × 104 CFU/day) was administered orally from postnatal day 3. Pulmonary outcomes were assessed by histological analyses including mean alveolar volume, radial alveolar count, von Willebrand factor immunofluorescence staining, and TUNEL assay. Gut and pulmonary microbiome composition was evaluated by 16S rRNA sequencing, and intestinal butyrate and glutathione levels were measured. Results: Probiotic supplementation significantly improved alveolarization and pulmonary vascular endothelial marker expression, with a concurrent reduction in apoptotic cell death and ED1-positive cell accumulation compared with the HC group (all p < 0.05). Hyperoxia-induced phylum-level shifts in Firmicutes and Bacteroidetes abundance were partially attenuated in the HP group, although alpha- and beta-diversity indices and genus- and species-level analyses did not show a consistent pattern of restoration. Intestinal butyrate and glutathione levels were significantly lower in the HC group than in the NC group (p < 0.05). Concentrations in the HP group were numerically higher than in the HC group but did not differ significantly from either the NC or HC group. In lung tissue, SOD2 gene expression was significantly increased in the HP group compared with both the NC and HC groups (p < 0.05). Conclusions: Oral L. reuteri DSM 17938 attenuates hyperoxia-induced lung injury in a neonatal rat model, with increased pulmonary SOD2 gene expression, alongside a consistent directional trend in related antioxidant pathway genes, and phylum-level gut microbiome changes identified as potential contributing mechanisms. These findings provide preclinical evidence for a potential protective effect of this commercially available probiotic strain against hyperoxia-induced lung injury, warranting further investigation before translation to clinical prevention strategies for BPD.