Investigating the Mechanism of Pulmonary Toxicity in SD Rats Mediated by the Microbiota-Gut-Lung Axis Due to Podophyllotoxin Based on the Concept of the Toxicological Evidence Chain (TEC)
We conducted comprehensive analyses, including observations of rat injury phenotypes, assessments of pulmonary pathological changes, detection of pro-inflammatory factors, as well as in-depth analyses of pulmonary and gastrointestinal microbiomes and metabolomics. Concurrently, PPT exposure disrupts both intestinal and pulmonary microbiomes, with a significant enrichment of Morganella in the pulmonary microbiota, which negatively correlates with beneficial metabolites such as Propanoic acid, Hexanoic acid, Butanoic acid, and Acetic acid, and probiotics like Marvinbryantia and Enterorhabdus, while showing a significant positive correlation with pathogens Escherichia-Shigella and Bilophila. The substantial enrichment of Morganella leads to imbalances in the abundance and diversity of major bacterial phyla and genera in the lung microbiome, triggering downstream immune responses and abnormalities in short-chain fatty acid metabolism, potentially leading to pulmonary toxicity. This study offers new insights into the mechanisms of PPT-induced pulmonary toxicity, highlights the role of the "Lung-Gut Axis," and provides avenues for therapeutic intervention.