Scholarlink

Background <p>The increased use of nanosilica (SiO<sub>2</sub> NPs) poses a safety risk to public health. Current research on the tissue distribution and microbiota-gut-liver crosstalk toxicity of orally ingested SiO<sub>2</sub> NPs remains poorly understood. In this study, we examined the distribution of SiO<sub>2</sub> NPs by gavage in major organs as well as liver senescence and fibrotic injury induced by microbiota-gut-liver crosstalk following the sub-chronic oral ingestion thereof. In addition, probiotics were administered to investigate their protective potential against SiO<sub>2</sub> NPs-induced hepatotoxicity.</p> Results <p>Our results showed that C57BL/6J mice that received orally administered SiO<sub>2</sub> NPs for 12 w exhibited gut dysbiosis, imbalance of metabolites (short-chain fatty acids and lactate), intestinal barrier damage, and disruption of gut homeostasis. Furthermore, ICP-OES revealed the silicon accumulation in the Liver, with 165% increase compared to the control, higher than that in other tissue. Liver exhibited functional abnormalities and underwent Lipid deposition, autophagy, senescence and fibrosis. 16S rRNA sequencing analysis demonstrated that SiO<sub>2</sub> NPs reduced the abundance of probiotic <i>Muribaculum</i> and <i>Ligilactobacillus</i>, while increasing that of pathogenic <i>Helicobacter</i>. Notably, supplementation with probiotics remodelled the gut microbiome, particularly corrected the microbial communities disrupted by SiO<sub>2</sub> NPs, increased the proliferation of other probiotics, and reduced harmful bacteria. Moreover, the results of Masson staining, Nile red staining, and immunofluorescence showed that probiotic supplementation ameliorated liver lipid deposition, senescence, and fibrosis induced by the oral ingestion of SiO<sub>2</sub> NPs. Mechanistically, the TLR4/NF-κB and caspase-3-cytochrome C pathways may be involved in SiO<sub>2</sub> NPs-induced hepatotoxicity and probiotic regulation.</p> Conclusions <p>Continuous oral ingestion of SiO<sub>2</sub> NPs induced liver-specific accumulation, and caused abnormal deposition of liver lipids, senescence and fibrosis via microbiota-gut-liver crosstalk. Microbial therapy involving probiotic supplementation mitigated SiO<sub>2</sub> NPs-induced hepatotoxicity and exerted protective effects. This study provides a scientific reference for the rational application, risk management, and prevention of the harmful effects caused by SiO<sub>2</sub> NPs.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Orally ingested nanosilica causes liver-specific accumulation and induces liver senescence and fibrosis via the microbiota-gut-liver axis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月10日

查看全文
  • Xiaofei Han,
  • Lisha Du,
  • Yanjie Dou,
  • Huan Wang,
  • Mengyuan Lv,
  • Longxing Wang,
  • Jun Xiao,
  • Jiajun Yin,
  • Ju Wu

摘要

Background

The increased use of nanosilica (SiO2 NPs) poses a safety risk to public health. Current research on the tissue distribution and microbiota-gut-liver crosstalk toxicity of orally ingested SiO2 NPs remains poorly understood. In this study, we examined the distribution of SiO2 NPs by gavage in major organs as well as liver senescence and fibrotic injury induced by microbiota-gut-liver crosstalk following the sub-chronic oral ingestion thereof. In addition, probiotics were administered to investigate their protective potential against SiO2 NPs-induced hepatotoxicity.

Results

Our results showed that C57BL/6J mice that received orally administered SiO2 NPs for 12 w exhibited gut dysbiosis, imbalance of metabolites (short-chain fatty acids and lactate), intestinal barrier damage, and disruption of gut homeostasis. Furthermore, ICP-OES revealed the silicon accumulation in the Liver, with 165% increase compared to the control, higher than that in other tissue. Liver exhibited functional abnormalities and underwent Lipid deposition, autophagy, senescence and fibrosis. 16S rRNA sequencing analysis demonstrated that SiO2 NPs reduced the abundance of probiotic Muribaculum and Ligilactobacillus, while increasing that of pathogenic Helicobacter. Notably, supplementation with probiotics remodelled the gut microbiome, particularly corrected the microbial communities disrupted by SiO2 NPs, increased the proliferation of other probiotics, and reduced harmful bacteria. Moreover, the results of Masson staining, Nile red staining, and immunofluorescence showed that probiotic supplementation ameliorated liver lipid deposition, senescence, and fibrosis induced by the oral ingestion of SiO2 NPs. Mechanistically, the TLR4/NF-κB and caspase-3-cytochrome C pathways may be involved in SiO2 NPs-induced hepatotoxicity and probiotic regulation.

Conclusions

Continuous oral ingestion of SiO2 NPs induced liver-specific accumulation, and caused abnormal deposition of liver lipids, senescence and fibrosis via microbiota-gut-liver crosstalk. Microbial therapy involving probiotic supplementation mitigated SiO2 NPs-induced hepatotoxicity and exerted protective effects. This study provides a scientific reference for the rational application, risk management, and prevention of the harmful effects caused by SiO2 NPs.

Graphical Abstract