Pulmonary fibrosis alters gut microbiota and associated metabolites in mice: An integrated 16S and metabolomics analysis

The "gut-lung axis" reflects intimate connection and bidirectional effect between gut and lung, involving numerous lung diseases. Pulmonary fibrosis is a progressive interstitial lung disease with high fatality rate, so far, its association with gut remains unexplored. We investigated the correlation between pulmonary fibrosis and gut microbiota. We collected feces from two pulmonary fibrotic models respectively, and performed a combinatory study using 16S rDNA sequencing and non-targeted metabonomics. Correlation matrix was used to indicate the correlation between microbiome, metabolites and fibrotic indicators, and the possibility of gut microbiota in identifying pulmonary fibrosis was assessed by ROC analysis. 412 genera of microflora and 26 kinds of metabolites were synchronously altered with same trend in two models but differed observably with control. Among these, 7 microorganisms and 9 metabolites were the typical representatives, which were correlated significantly and highly correlated with fibrotic indicators shown by correlation matrix. ROC analysis indicated that it was dependable to identify pulmonary fibrosis by using gut microorganisms and metabolites in both models (AUC > 0.85, p < 0.01). In summary, our findings first revealed a previously unknown correlation between gut and pulmonary fibrosis in mouse models, which creates novel insights of the interaction between pulmonary fibrosis and gut microbiota.