Early environmental exposure to oxytetracycline in Danio rerio may contribute to neurobehavioral abnormalities in adult zebrafish

• Published in: The Science of the total environment Vol. 882; p. 163482
• Main Authors: Yu, Kan, Qiu, Yushu, Shi, Yi, Yu, Xiaogang, Zhou, Baosong, Sun, Tong, Wu, Yuhang, Xu, Shanshan, Chen, Lei, Shu, Qiang, Huang, Lisu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-07-2023
• Subjects: Animals; Anti-Bacterial Agents - toxicity; Early life; Environmental oxytetracycline; Gastrointestinal Microbiome; Gut microbiota; Larva; Neurobehavior; Oxytetracycline - toxicity; Persistent effect; RNA, Ribosomal, 16S - genetics; Zebrafish - physiology; PCoA; Gut microbiota; ORF; OTUs; LDA; DMs; BP; DEGs; QC; PPAR; FDR; clstn2; KEGG; MF; crybb2; Persistent effect; GO; Early life; NMDS; NeuN; Environmental oxytetracycline; Neurobehavior; Dpf; Hpf; OTC; rpl8
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2023.163482

The common antibiotic oxytetracycline (OTC) is nowadays commonly found in natural aquatic environments. However, the underlying mechanisms of low-dose OTC exposure and its neurotoxic effects on aquatic animals remain unknown. In this study, we exposed zebrafish larvae to environmental concentrations of OTC in early life and performed neurobehavioral, 16S rRNA gene sequencing, and transcriptomic analyses. OTC exposure resulted in hyperactivity of larvae and a significant reduction in the number of neurons in the midbrain. The expression levels of 15 genes related to neural function changed. Additionally, the composition of 65 genera of the gut microbiota of larvae was altered, which may be one of the reasons for the abnormal neural development. We further studied the long-term outcomes among adult fish long after cessation of OTC exposure. OTC treatment caused adult fish to be depressive and impulsive, symbolizing bipolar disorder. Adult fish exposed to OTC had significantly fewer neurons and their gut bacteria composition did not recover 104 days after terminating OTC exposure. Finally, we analyzed the correlation between the gut microbiota of larvae, genes related to neural function, and metabolites of adult fish brain tissue. The results showed that the abundance of several members of the biome in larvae was related to the transcription levels of genes related to neural function, which were related to the metabolic levels in the adult brain. In conclusion, our study showed that early-life exposure to environmental concentrations of OTC can lead to persistent neurobehavioral abnormalities until adulthood through dysbiosis in the gut microbiota.
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•Low-dose OTC exposure in early life results in abnormal nerve behavior of larvae.•Early-life OTC exposure affects larvae's gut microbiome composition.•After halting OTC exposure, metabolic changes were observed in adult brain tissue.•Changes to neurons and gut microbiota in adult zebrafish were irreversible.•OTC may affect neurodevelopment by changing the gut microbiome composition.