Background <p>Sodium ρ-perfluorous nonenoxybenzene sulfonate (OBS), categorised as an emerging perfluoroalkyl substance (PFAS), is considered as an alternative to legacy PFAS, such as perfluorooctanoic acid (PFOA), a persistent organic pollutant with known hepatotoxic effects. The comparative toxicity of OBS and PFOA, particularly in the liver and intestines, remains understudied.</p> Objectives <p>We focussed on the distinct effects of PFOA and OBS on liver and intestinal microbes via multi-omics (transcriptome, untargeted metabolomics), histopathology and RT-qPCR analysis.</p> Results <p>PFOA and OBS increased liver weight and serum ALT levels (<i>P</i> &lt; 0.01), but OBS uniquely elevated AST levels (<i>P</i> &lt; 0.01). Multi-omics analysis revealed differential effects on liver gene expression and metabolism. OBS exposure was linked to disrupted linoleic acid metabolism, with decreased linoleic acid levels and increased 12,13-DHOME ((9Z)-12,13-dihydroxyoctadec-9-enoic acid) levels, whereas PFOA affected arachidonic acid metabolism. Both PFASs compromised the intestinal barrier, as evidenced by reduced goblet cells, downregulated mucin genes and increased proinflammatory cytokines. They also altered the gut microbiota composition and reduced SCFA levels (<i>P</i> &lt; 0.01).</p> Conclusion <p>PFOA and OBS exposure detrimentally affects the intestinal health and causes liver damage, with OBS inducing more severe liver injury. Liver damage caused by OBS exposure is associated with linoleic acid metabolism disorder and 12,13-DHOME production. As a new PFAS, OBS toxicity warrants further scrutiny.</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

Multi-omics analysis revealed the differential effects and mechanisms of PFOA and OBS exposure on liver and intestinal function

  • Minjie Yu,
  • Ruochen Ren,
  • Hongbo Zeng,
  • Meng Hou,
  • Kaiyi Jiang,
  • Caihong Hu,
  • Yingping Xiao,
  • Wentao Lyu

摘要

Background

Sodium ρ-perfluorous nonenoxybenzene sulfonate (OBS), categorised as an emerging perfluoroalkyl substance (PFAS), is considered as an alternative to legacy PFAS, such as perfluorooctanoic acid (PFOA), a persistent organic pollutant with known hepatotoxic effects. The comparative toxicity of OBS and PFOA, particularly in the liver and intestines, remains understudied.

Objectives

We focussed on the distinct effects of PFOA and OBS on liver and intestinal microbes via multi-omics (transcriptome, untargeted metabolomics), histopathology and RT-qPCR analysis.

Results

PFOA and OBS increased liver weight and serum ALT levels (P < 0.01), but OBS uniquely elevated AST levels (P < 0.01). Multi-omics analysis revealed differential effects on liver gene expression and metabolism. OBS exposure was linked to disrupted linoleic acid metabolism, with decreased linoleic acid levels and increased 12,13-DHOME ((9Z)-12,13-dihydroxyoctadec-9-enoic acid) levels, whereas PFOA affected arachidonic acid metabolism. Both PFASs compromised the intestinal barrier, as evidenced by reduced goblet cells, downregulated mucin genes and increased proinflammatory cytokines. They also altered the gut microbiota composition and reduced SCFA levels (P < 0.01).

Conclusion

PFOA and OBS exposure detrimentally affects the intestinal health and causes liver damage, with OBS inducing more severe liver injury. Liver damage caused by OBS exposure is associated with linoleic acid metabolism disorder and 12,13-DHOME production. As a new PFAS, OBS toxicity warrants further scrutiny.