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Objective To investigate the changes in gut microbiota, serum metabolites, and differentially expressed genes (DEGs) in the lung tissue of the mouse model of pulmonary fibrosis and explore the potential associations via multi-omics analysis. Methods A mouse model of pulmonary fibrosis was established by the dynamic inhalation exposure method and evaluated. Metagenomic sequencing was performed to analyze the microecological changes in cecal contents. Untargeted metabolomics was employed to detect serum metabolite alterations, and transcriptomic sequencing was conducted to profile DEGs in the lung tissue. Bioinformatics methods were comprehensively used to explore correlations and potential functional modules among differential microbial taxa, metabolites, and genes. Results Pathological changes of pulmonary fibrosis were successfully induced in the model mice, accompanied by the upregulated expression of transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and fibrosis-related genes in the lung tissue. Omics results indicated the presence of gut microbiota dysbiosis, serum amino acid metabolic disorder, and lung transcriptome remodeling in the model mice. Correlation analysis demonstrated that the four differential bacterial species were strongly correlated with multiple serum metabolites, among which Akkermansia muciniphila and Ligilactobacillus murinus were jointly associated with 22 differential metabolites. A cross-omics network was constructed with these 22 differential metabolites and DEGs. Topological analysis identified five key subnetworks: (1) Inosine triphosphate serves as a phosphate donor and is converted to inosine diphosphate via multiple pathways; (2) Uridine triphosphate (UTP) undergoes an amination reaction to form cytidine triphosphate (CTP); (3) Serine/threonine-protein kinase 11, Fas-activated serine/threonine kinase, and cyclic GMP-dependent protein kinase act as core kinase nodes; (4) The reaction between serine and homocysteine bridges the metabolic pathways of methionine and cysteine; (5) Prostaglandin H2 is catalytically converted into thromboxane A2. Conclusion There are significant statistical correlations among gut microbiota, serum metabolites, and DEGs in the lung tissue in the mouse model of pulmonary fibrosis. We identify the core association network and potential functional modules, which provide references for the subsequent mechanism exploration of pulmonary fibrosis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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