The Gut Microbiome and Metabolomics Profiles of Dust-exposed Rats

BACKGROUND: Limited treatments for silicosis necessitate further study of pneumoconiosis characteristics and pathophysiology. This study employs metabolomics to investigate metabolite changes and identify biomarkers for understanding pneumoconiosis pathogenesis. METHODS: We explored pneumoconiosis pathogenesis through the lens of intestinal flora, using 18 healthy SPF male SD rats divided into three groups: control, coal dust, and silica. After dust exposure, metabolite changes were analyzed to identify metabolic markers and pathways. We assessed the relationship between intestinal flora and silicosis, aiming to provide early diagnostic evidence. Rats were exposed to coal dust, silica, or sterile saline for 8 weeks, after which blood, lung tissue, and feces were collected. Lung pathology was assessed, and inflammatory factors (IL-6, IL-11) were measured. 16S rDNA sequencing and UHPLC-QTOFMS metabolomics were used to analyze intestinal flora and fecal metabolites. RESULTS: After 8 weeks of dust exposure, silica-exposed rats showed significantly reduced weight and elevated serum IL-6 and IL-11 levels compared to controls (P < 0.05). Lung tissue pathology revealed normal alveolar structure in controls, whereas silica group rats exhibited lung damage, intensified inflammation, and silicon nodule formation. Coal dust group rats showed lung tissue changes with fibroblast aggregation. α diversity analysis showed a decreased Shannon index and increased Simpson index in the coal dust group, and a decreased Simpson index in the silica group, suggesting altered intestinal flora. β diversity analysis confirmed significant differences in gut microbiota between dust-exposed groups and controls. Metabolomics identified 11 differential metabolites in rat feces, meeting criteria of Fold change > 2, VIP > 1, and P < 0.05, indicating metabolic changes post-exposure. CONCLUSION: Dust exposure disrupts intestinal flora and metabolic state, with potential metabolic markers identified in both coal dust and silica groups, implicating fructose and mannose metabolism in coal dust exposure and sphingolipid metabolism in silica exposure. This study provides new insights into the pathogenesis of pneumoconiosis and potential biomarkers for early diagnosis.