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

Mar 28, 2026Fish physiology and biochemistry

Vitamin C changes chromium-induced disruptions across the gut bacteria, gut, and brain systems in adult zebrafish

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Abstract

Vitamin C reduced the neurotoxic and enterotoxic effects of 2 mg/L hexavalent chromium in adult zebrafish over a 60-day exposure period.

Vitamin C modulated neuropathological lesions and intestinal cell changes caused by hexavalent chromium.
Microbiota analysis revealed that Vitamin C partially restored microbial balance disrupted by chromium exposure.
Transcriptomic analysis identified 78 genes in the brain linked to neurological function and cancer pathways affected by chromium.
In the intestines, 52 genes associated with viral infection and neural signaling pathways were also impacted.
Pathogenic Aeromonas bacteria were correlated with downregulated genes in the brain, while beneficial Pseudomonas were linked to upregulated genes in the intestines.

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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.

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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

Abstract

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