Dihydroquercetin Attenuates Silica‐Induced Pulmonary Fibrosis by Modulating the Gut Microbiota and the Serum Metabolites in Mice

Dihydroquercetin (DHQ), a crucial dihydroflavone found in nature, demonstrates notable antioxidant, anti‐inflammatory, and antifibrotic effects. Nevertheless, the impact on the gut microbiome and metabolites associated with silicosis remains unclear. Hence, the objective of this research was to examine how DHQ impacts silicosis and the associated mechanisms through analyzing gut microbiota with 16S rRNA sequencing and conducting serum metabolomic analysis. The findings of our study showed that administering DHQ significantly attenuated the level of inflammation and fibrosis in the lung tissues of C57BL/6 mice exposed to silica. Furthermore, DHQ clearly raised the amount of Muribaculaceae, while diminishing the amount of Lactobacillus . DHQ treatment significantly decreased the sphingomyelin, arachidonic acid and its metabolites. Significantly, the correlation analysis showed that the influence of DHQ on the arachidonic acid metabolism, steroid hormone biosynthesis, and sphingolipid signaling pathways were linked to changes in the levels of Muribaculaceae and Lactobacillus in the gut microflora. In summary, our research demonstrated that DHQ can attenuated inflammation and lung fibrosis caused by silica exposure in the C57BL/6 mice, potentially by modulating the gut microbiota and serum metabolites. (1) DHQ can attenuate silica‐induced inflammation and pulmonary fibrosis in the C57BL/6 mice. (2) The beneficial effects of DHQ were primarily attributed to the alteration of gut microbiota (particularly Muribaculaceae and Lactobacillus) mediated by serum metabolites.