Investigation of the mechanism of silica-induced pulmonary fibrosis: The role of lung microbiota dysbiosis and the LPS/TLR4 signaling pathway

The widespread manufacture of silica and its extensive use, and potential release of silica into the environment pose a serious human health hazard. Silicosis, a severe global public health issue, is caused by exposure to silica, leading to persistent inflammation and fibrosis of the lungs. The underlying pathogenic mechanisms of silicosis remain elusive. Lung microbiota dysbiosis is associated with the development of inflammation and fibrosis. However, limited information is currently available regarding the role of lung microbiota in silicosis. The study therefore is designed to conduct a comprehensive analysis of the role of lung microbiota dysbiosis and establish a basis for future investigations into the potential mechanisms underlying silicosis. Here, the pathological and biochemical parameters were used to systematically assessed the degree of inflammation and fibrosis following silica exposure and treatment with combined antibiotics. The underlying mechanisms were studied via integrative multi-omics analyses of the transcriptome and microbiome. Analysis of 16S ribosomal DNA revealed dysbiosis of the microbial community in silicosis, characterized by a predominance of gram-negative bacteria. Exposure to silica has been shown to trigger lung inflammation and fibrosis, leading to an increased concentration of lipopolysaccharides in the bronchoalveolar lavage fluid. Furthermore, Toll-like receptor 4 was identified as a key molecule in the lung microbiota dysbiosis associated with silica-induced lung fibrosis. All of these outcomes can be partially controlled through combined antibiotic administration. The study findings demonstrate that the dysbiosis of lung microbiota enhances silica-induced fibrosis associated with the lipopolysaccharides/Toll-like receptor 4 pathway and provided a promising target for therapeutic intervention of silicosis. [Display omitted] •Lung microbiota dysbiosis is essential for silica-induced pulmonary fibrosis.•Lung microbiota dysbiosis augments silica-induced fibrosis via the LPS/TLR4 pathway.•Combined antibiotic administration alleviates silica-induced lung fibrosis.