Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota
Silicosis is a prevalent occupational disease marked by progressive pulmonary fibrosis. Despite its significant health burden, the pathogenesis of silicosis remains unclear, and no specific therapeutic drugs are available. In this study, we developed a novel intervention strategy targeting gut micro...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325003057 |
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| Summary: | Silicosis is a prevalent occupational disease marked by progressive pulmonary fibrosis. Despite its significant health burden, the pathogenesis of silicosis remains unclear, and no specific therapeutic drugs are available. In this study, we developed a novel intervention strategy targeting gut microbiota and investigated its underlying mechanisms. Using 16S rRNA gene sequencing, we observed significant gut microbiota dysbiosis in silicosis rats at different times (1–8 weeks), notably characterized by altered relative abundance of Ruminococcus and Lactobacillus. Fecal microbiota transplantation altered the gut microbiota structure of silicosis rats, alleviated silica-induced lung histopathological injury, with LEfSe analysis identifying Bifidobacterium as a potential biomarker. Treatment with Bifidobacterium reduced the level of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and fibrosis markers (collagen III, α-SMA and vimentin) in the lungs of silicosis rats, accompanied with increased serum acetic acid levels. Acetate, a major metabolite of Bifidobacterium, demonstrated similar protective effects against silicosis in this study, suggesting its role as a key mediator of Bifidobacterium action in the lungs. Both Bifidobacterium and acetate significantly upregulated Sirt1 in intestinal and lung tissues, while Sirt1 inhibition diminished their benefits to silicosis. As a widely studied histone deacetylase, Sirt1 was proven to be markedly reduced in the lungs of silicosis rats in this study. EX-527, a potent Sirt1 inhibitor, could worsen silicosis damage by upregulating the level of TGF-β1 and the degree of Smad2/3 acetylation. Our study highlights the efficacy of postbiotics, such as Bifidobacterium and acetate, and identifies Sirt1 as a promising target for silicosis treatment. |
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| ISSN: | 0147-6513 |