Low-dose triclosan induces neurotoxicity in zebrafish via gut microbiota disruption

Triclosan (TCS), a broad-spectrum antibacterial agent, is widely detected in environmental and human samples, yet its neurotoxic risks and mechanisms following long-term environmental exposure remain unclear-particularly the role of gut microbiota. Using germ-free zebrafish and fecal microbiota transplantation, we established a causal link between TCS-induced gut dysbiosis and neurotoxicity. Integrating transcriptomics, 16S rRNA sequencing, and gut-derived metabolite transplantation, we elucidated the underlying molecular mechanisms. Three-month exposure to environmentally relevant TCS concentrations significantly enriched gut Proteobacteria, increasing lipopolysaccharide (LPS) levels. LPS subsequently crossed the damaged blood-brain barrier via the gut-brain axis, triggering neuroinflammation and behavioral abnormalities in female zebrafish. Notably, TCS exhibited dose-dependent neurotoxicity: low doses (0.4 and 4.0 μg/L) acted primarily through gut microbiota disruption, while high-dose (40 μg/L) effects involved both microbiota-dependent and independent pathways. This study provides new insights into the neurotoxic mechanisms of TCS and highlights the critical role of gut microbiota in mediating its effects. However, this study was conducted exclusively in female zebrafish, and further investigations in males are warranted to assess potential sex differences.