Gut dysbiosis mediates neurotoxic effects of environmentally relevant tylosin exposure in adult zebrafish

作者：Wenbo Li, N. Wang, Donghao Lyu, Xiaogang Yu, Xiaolong He, Yu Kan, Yushu Qiu, Xianting Jiao · 发表于：Ecotoxicology and Environmental Safety · 年份：2025 · DOI：10.1016/j.ecoenv.2025.118960 · 被引用次数：5 · 研究领域：Tryptophan and brain disorders、Neuroinflammation and Neurodegeneration Mechanisms、Stress Responses and Cortisol

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...