The Impact of Uranium-Induced Pulmonary Fibrosis on Gut Microbiota and Related Metabolites in Rats.

Background/

Objectives

This study aimed to evaluate the effects of lung injury induced by insoluble uranium oxide particles on gut microbiota and related metabolites in rats.

Methods

The rats were randomly divided into six UO2 dose groups. A rat lung injury model was established through UO2 aerosol. The levels of uranium in lung tissues were detected by ICP-MS. The expression levels of the inflammatory factors and fibrosis indexes were measured by enzyme-linked immunosorbent assay. Paraffin embedding-based hematoxylin & eosin staining for the lung tissue was performed to observe the histopathological imaging features. Metagenomic sequencing technology and HM700-targeted metabolomics were conducted in lung tissues.

Results

Uranium levels in the lung tissues increased with dose increase. The expression levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Collagen I, and Hydroxyproline (Hyp) in rat lung homogenate increased with dose increase. Inflammatory cell infiltration and the deposition of extracellular matrix were observed in rat lung tissue post-exposure. Compared to the control group, the ratio of Firmicutes and Bacteroides in the gut microbiota decreased, the relative abundance of Akkermansia_mucinphila decreased, and the relative abundance of Bacteroides increased. The important differential metabolites mainly include αlpha-linolenic acid, gamma-linolenic acid, 2-Hydroxybutyric acid, Beta-Alanine, Maleic acid, Hyocholic acid, L-Lysine, L-Methionine, L-Leucine, which were mainly concentrated in unsaturated fatty acid biosynthesis, propionic acid metabolism, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, and other pathways in the UO2 group compared to the control group.

Conclusions

These findings suggest that uranium-induced lung injury can cause the disturbance of gut microbiota and its metabolites in rats, and these changes are mainly caused by Akkermansia_mucinphila and Bacteroides, focusing on unsaturated fatty acid biosynthesis and the propionic acid metabolism pathway.