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<p>Hexavalent chromium (Cr(VI)) is a widely present carcinogenic environmental pollutant, has demonstrated well-documented neurotoxic and enterotoxic effects in aquatic organisms, yet limited research exists on mitigating its toxicity through brain-gut-microbiota axis regulation. Vitamin C (VC), a potent antioxidant and immunomodulator, has shown potential in mitigating heavy metal toxicity. Nevertheless, how VC regulates Cr(VI) toxicity via the brain-gut-microbiota axis remains unclear. To investigate VC’s potential protective role, adult zebrafish were divided into three groups: control, 2&#xa0;mg/L Cr(VI), 2&#xa0;mg/L Cr(VI) + 2&#xa0;mg/L VC groups, with a 60-day exposure period. Histopathological changes, 16S rRNA, intestinal, and brain RNA-sequencing were examined. The results showed that VC modulated neuropathological lesions and intestinal goblet cell vacuolization caused by Cr(VI). 16S rRNA further confirmed VC partially modulated microbiota homeostasis. Transcriptomic analysis identified 78 differentially expressed genes (DEGs) in the brain; KEGG enrichment analysis showed these DEGs are associated with neurological function and gastrointestinal carcinogenesis pathways. Concurrently, 52 DEGs in intestinal were linked to viral infection and neural signaling pathways. Correlation analyses demonstrated pathogenic <i>Aeromonas</i> was positively correlated with <i>ace</i>, <i>enpep</i>, <i>prss1</i>, <i>asah2</i>, and <i>cd36</i> in the brain, those are downregulated DEGs, whereas beneficial <i>Pseudomonas</i> was positively correlated with <i>c6ast4</i> and <i>nfe211b</i> in intestinal, they are upregulated DEGs. This indicates <i>Aeromonas</i> and <i>Pseudomona</i>s could act as key mediators through which VC reduces Cr(VI)-induced neuro- and immunotoxicity. Collectively, these findings provide mechanistic insights into VC’s protective role against parallel disruptions along the microbiota-gut-brain axis, suggesting its potential as a waterborne supplement for reducing Cr(VI) toxicity in aquaculture system.</p>

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Vitamin C modulates Cr(VI)-induced parallel disruptions along the microbiota-gut-brain axis in adult zebrafish: insights from transcriptomic and microbiome analysis

  • 期刊论文

  • 发表日期：

    2026年3月28日

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  • Guan-Ling Lu,
  • Ying-Hui Zhao,
  • Yu-Qi Ruan,
  • Jing Ning,
  • Lu Wei

摘要

Hexavalent chromium (Cr(VI)) is a widely present carcinogenic environmental pollutant, has demonstrated well-documented neurotoxic and enterotoxic effects in aquatic organisms, yet limited research exists on mitigating its toxicity through brain-gut-microbiota axis regulation. Vitamin C (VC), a potent antioxidant and immunomodulator, has shown potential in mitigating heavy metal toxicity. Nevertheless, how VC regulates Cr(VI) toxicity via the brain-gut-microbiota axis remains unclear. To investigate VC’s potential protective role, adult zebrafish were divided into three groups: control, 2 mg/L Cr(VI), 2 mg/L Cr(VI) + 2 mg/L VC groups, with a 60-day exposure period. Histopathological changes, 16S rRNA, intestinal, and brain RNA-sequencing were examined. The results showed that VC modulated neuropathological lesions and intestinal goblet cell vacuolization caused by Cr(VI). 16S rRNA further confirmed VC partially modulated microbiota homeostasis. Transcriptomic analysis identified 78 differentially expressed genes (DEGs) in the brain; KEGG enrichment analysis showed these DEGs are associated with neurological function and gastrointestinal carcinogenesis pathways. Concurrently, 52 DEGs in intestinal were linked to viral infection and neural signaling pathways. Correlation analyses demonstrated pathogenic Aeromonas was positively correlated with ace, enpep, prss1, asah2, and cd36 in the brain, those are downregulated DEGs, whereas beneficial Pseudomonas was positively correlated with c6ast4 and nfe211b in intestinal, they are upregulated DEGs. This indicates Aeromonas and Pseudomonas could act as key mediators through which VC reduces Cr(VI)-induced neuro- and immunotoxicity. Collectively, these findings provide mechanistic insights into VC’s protective role against parallel disruptions along the microbiota-gut-brain axis, suggesting its potential as a waterborne supplement for reducing Cr(VI) toxicity in aquaculture system.