Long-term oxytetracycline exposure potentially alters brain thyroid hormone and serotonin homeostasis in zebrafish.

The impact of oxytetracycline (OTC) exposure in water on the fish still remains unclear. We hypothesized OTC exposure could alter fish gut microbiome and affect thyroid hormone and serotonin homeostasis in the brain via "chemical-gut-brain" axis. Here, ∼2-month-old juvenile zebrafish (Danio rerio) was exposed to two concentrations of OTC (1 and 100 µg/L) for one month until adulthood. Thyroxine-associated gene analysis in the brain revealed that deiodinase 2 (DIO2), deiodinase 3 (DIO3), and thyroid hormone receptor beta (THRß) expression was significantly decreased. Quantification of thyroid hormones showed a decrease in triiodothyronine (T3) under OTC treatment, which agrees with reduced activity of DIO2. For the serotonin (5-HT) synthesis, the expression of tryptophan hydroxylase (TPH2) was 41 % and 9.3 % of the control group for 1 and 100 µg/L OTC exposed groups; respectively. The intestinal 16S rRNA analysis revealed an increased abundance of Fusobacteria and Proteobacteria, while Actinobacteria was decreased significantly. The altered microbial balance between Proteobacteria and Firmicutes have been previously reported to affect nutrient uptakes such as zinc, which can potentially reduce the activity of DIO2. In summary, this study suggests that long-term OTC exposure not only alters gut microbiome but also changes thyroid hormone and serotonin homeostasis.