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Updated: Jan 13, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Melatonin ameliorates bronchopulmonary dysplasia by modulating the NF-κB pathway via the gut microbiota-short-chain
Yue Wang1, Qing Zhang2, Qiuyue Luo2
1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
Objective:
To elucidate the mechanism by which melatonin ameliorates bronchopulmonary dysplasia (BPD) via modulation of gut microbiota and its metabolite, short-chain fatty acids (SCFAs).
Methods:
A bleomycin-induced BPD mouse model was developed. Post-melatonin intervention, a comprehensive multi-omics approach, including metagenomics, 16S rRNA sequencing, untargeted metabolomics, and RNA transcriptomics, was employed alongside butyrate supplementation experiments to assess changes in alveolar architecture, oxidative stress, inflammatory cytokine levels, and the NF-κB signaling pathway. In vitro experiments utilizing human bronchial epithelial cells (BEAS-2B) and analyses of publicly available single-cell RNA sequencing data from infant lung tissues were conducted to further substantiate the underlying mechanisms.
Results:
The administration of melatonin led to a significant increase in the abundance of Ligilactobacillus murinus within the gut microbiota and enhanced the production of SCFAs. Notably, butyrate metabolites were found to be enriched in both serum and lung tissues, which was associated with the suppression of NF-κB pathway activation. Intervention with butyrate mirrored the therapeutic effects observed with melatonin, resulting in the alleviation of alveolar simplification, a reduction in oxidative damage and inflammatory cytokines, and the inhibition of both NF-κB pathway activation and pyroptosis in lung tissues. Additionally, in vitro experiments demonstrated that both melatonin and butyric acid directly inhibited NF-κB activation and pyroptosis in BEAS-2B cells injured by bleomycin. Analysis of single-cell data from human infant lungs revealed differential enrichment of genes related to NF-κB and pyroptosis in the bronchial and alveolar epithelial cells of patients with BPD, thereby underscoring the clinical significance of these pathways.
Conclusion:
Melatonin ameliorates BPD by modulating the gut microbiota-SCFA metabolic axis, which in turn suppresses NF-κB pathway activation and pyroptosis in lung tissues via systemic circulation. This finding suggests a novel therapeutic strategy for the treatment of BPD.
