Melatonin Alleviated Cadmium Induced Microbiota-Gut-Brain Disorder in Adult Zebrafish: Insights from Transcriptomic and Microbiome Analysis

Cadmium (Cd), a toxic heavy metal, poses significant threats to ecological and human health due to its neurotoxic and intestinal toxicity effects. However, the mechanisms by which Cd disrupts brain-gut axis interactions remain unclear, and strategies to mitigate these effects are limited. Melatonin (MT), known for its anti-inflammatory and antioxidant properties, has shown promise in counteracting heavy metal toxicity. This study investigated the protective mechanisms of MT against Cd-induced toxicity in adult zebrafish using histopathological analysis, 16S rRNA sequencing, RNA-sequencing, and qRT-PCR. Results showed that MT significantly alleviated Cd-induced structural damage in brain spongiosa and restored intestinal villi integrity. 16S rRNA sequencing revealed that MT reduced pathogenic bacteria (Acinetobacter, Achromobacter, Legionella) and increased beneficial bacteria (Aeromonas, Candidatus_Protochlamydia) in the gut microbiota. Transcriptomic analysis identified 31 DEGs (differentially expressed genes) in brain tissues, KEGG enrichment analysis showed these DEGs are associated with metabolism, oxidative stress, and neurodegenerative diseases pathways. Concurrently, 8 DEGs in intestinal were linked to Chemical carcinogenesis -reactive oxygen species and Oxidative phosphorylation signaling pathways. Correlation analysis showed that specific gut bacteria influenced the expression of neurotransmitter receptor and immune genes in the brain and intestine. These findings highlight MT's potential to mitigate Cd-induced neurotoxicity and immunotoxicity by modulating the gut microbiota, offering therapeutic insights for reducing Cd toxicity risks in aquaculture.