Imbalance of intestinal flora activates inflammatory response contributing to acute lung injury

Seawater drowning is a leading cause of accidental injury and death, and the resulting acute lung injury (ALI) is a serious clinical syndrome for which there are no effective treatments. This study aims to investigate the potential mechanism of seawater drowning-induced ALI.

Seawater drowning mouse models were constructed to assess lung injury. The hematoxylin & eosin (H&E) staining and fluorescent terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were used to observe the pathology of lung tissues and apoptosis, respectively. 16S rRNA and RNA-seq were performed to identify the structure of the intestinal microbes and the gene expression profiles of the lung tissue of the mice, respectively. The expression of cytokines was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by assay kits.

The results showed that seawater drowning aggravated lung injury and accelerated cell apoptosis in mice. Seawater exposure significantly altered the structure of mouse intestinal microbes, especially increasing the abundance of Firmicutes and decreasing that of Bacteroidota. Transcriptional upregulation of inflammatory responses in ALI mice was observed in the lung transcriptome, and differentially expressed genes were mainly enriched in inflammation-related pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, and chemokine signaling pathway, which were further confirmed by microbe-gene association analysis. Furthermore, inflammatory factors were up-regulated, oxidative stress molecule MDA was elevated, and SOD was decreased in the lung tissues of mice, suggesting that the imbalance of intestinal flora activated inflammatory and oxidative stress responses.

This study reveals the mechanism that intestinal microflora aggravates ALI by modulating inflammatory signaling pathways, depicting the landscape of the microbial-gene-lung axis and providing new insights into the use of gut flora as a therapeutic strategy for ALI.