Ecotoxicology and environmental safetyAug 31, 2025

Gut bacteria imbalance links tylosin exposure to brain harm in adult zebrafish

Updated Jan 20, 2026

Abstract

Chronic exposure to 5000 ng/L tylosin in adult zebrafish is associated with neurotoxic effects.

Behavioral tests revealed anxiety- and depression-like behaviors, such as reduced exploration and increased freezing.
Histopathological analysis showed neuronal degeneration indicated by decreased Nissl staining in critical brain regions.
Transcriptomic analysis identified significant changes in genes related to neuroinflammation, synaptic dysfunction, immune response, and steroid metabolism.
Alterations in gut microbiota composition and metabolic profiles were observed, particularly affecting tryptophan metabolism and steroid hormone synthesis.
Impaired intestinal barrier function was linked to a decrease in goblet cells and reduced expression of tight junction and mucin-2 proteins.
Fecal microbiota transplantation confirmed the role of altered gut microbiota in inducing behavioral changes, suggesting a microbiota-gut-brain axis involvement.

Simplified

Tylosin, a widely used veterinary macrolide antibiotic, raises environmental concerns due to its persistence and potential health risks. However, the neurotoxic effects of chronic low-dose tylosin exposure remain unclear. This study assessed the neurotoxicity of chronic exposure to environmentally relevant tylosin concentrations (5000 ng/L) in adult zebrafish. Behavioral tests indicated anxiety- and depression-like behaviors, including reduced exploration and increased freezing. Histopathology revealed neuronal degeneration, evidenced by decreased Nissl staining in key brain areas. Transcriptomic analysis identified significant changes in genes related to neuroinflammation, synaptic dysfunction, immune response, and steroid metabolism. Multi-omics approaches further showed substantial alterations in gut microbiota composition and metabolic profiles, particularly involving tryptophan metabolism and steroid hormone synthesis. These gut changes correlated with impaired intestinal barrier function, including fewer goblet cells and reduced tight junction and mucin-2 protein expression. Fecal microbiota transplantation confirmed the role of altered gut microbiota in inducing anxiety- and depression-like behaviors, highlighting microbiota-gut-brain axis involvement. Molecular docking identified microbial metabolites (MG 20:4, 2E-dodecenedioic acid, Ononin) interacting with critical neurodevelopmental and stress-response proteins (LRAT, BHLHE40, HSPA5), potentially linking microbiota shifts to brain dysfunction. Our results demonstrate that chronic environmental tylosin exposure induces neurotoxicity through gut dysbiosis and compromised intestinal barriers, disrupting essential neuroactive pathways. These findings emphasize the importance of considering microbiota-gut-brain axis disruption in environmental antibiotic risk assessments.

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