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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Elsevier
2025-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325003057 |
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| author | Weiliang Zhang Xuejie Qi Mingming Han Qiang Jia Xixi Li Wenhui Yin Yanhui Wang Heng Wu Hua Shao Cheng Peng Chongyi Su Linlin Sai |
| author_facet | Weiliang Zhang Xuejie Qi Mingming Han Qiang Jia Xixi Li Wenhui Yin Yanhui Wang Heng Wu Hua Shao Cheng Peng Chongyi Su Linlin Sai |
| author_sort | Weiliang Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e5ec82e008ef4aebb361290612c65623 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-e5ec82e008ef4aebb361290612c656232025-08-20T02:52:27ZengElsevierEcotoxicology and Environmental Safety0147-65132025-03-0129211796910.1016/j.ecoenv.2025.117969Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiotaWeiliang Zhang0Xuejie Qi1Mingming Han2Qiang Jia3Xixi Li4Wenhui Yin5Yanhui Wang6Heng Wu7Hua Shao8Cheng Peng9Chongyi Su10Linlin Sai11Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong, ChinaDepartment of Health Statistics, School of Public Health, Shandong Second Medical University, Weifang, Shandong, ChinaShandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaShandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaShandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaShandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaShandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong, ChinaShandong First Medical University & Shandong Academy of Medical Sciences, Shandong Academy of Occupational Health and Occupational Medicine, Jinan, Shandong, ChinaShandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaShandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China; Eusyn Institute of Health Science, Brisbane, QLD 4102, Australia; Shandong FMT Centre for Gut Microbiome Health, Jinan, Shandong, ChinaShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaShandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S0147651325003057SilicosisGut microbiotaBifidobacteriaAcetateSirt1 |
| spellingShingle | Weiliang Zhang Xuejie Qi Mingming Han Qiang Jia Xixi Li Wenhui Yin Yanhui Wang Heng Wu Hua Shao Cheng Peng Chongyi Su Linlin Sai Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota Ecotoxicology and Environmental Safety Silicosis Gut microbiota Bifidobacteria Acetate Sirt1 |
| title | Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota |
| title_full | Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota |
| title_fullStr | Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota |
| title_full_unstemmed | Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota |
| title_short | Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota |
| title_sort | activation of sirt1 by acetate alleviates silicofibrosis contribution of the gut microbiota |
| topic | Silicosis Gut microbiota Bifidobacteria Acetate Sirt1 |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325003057 |
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