Chronic Exposure to Environmentally Relevant Concentrations of Tetracycline Perturbs Gut Homeostasis in Zebrafish

The prevalence of residual antibiotics is a global threat to human health. Less is known about the potential health effects of residual antibiotics in freshwater systems. Here, zebrafish were used to explore chronic effects of environmentally relevant concentrations (ERCs) of tetracycline (TC). Although chronic exposure to TC did not significantly alter the body weight of adult zebrafish, the exposed zebrafish parents exhibited substantial changes in gut microbiota composition and a reduced gut-weight ratio. Notably, male fish exposed to TC showed a significant decline of critical intestinal function-related metabolites (i.e., triglycerides, glucose, and free fat acid), while this was not observed in females, resulting in sex-dependency. The gut microbial composition of chronically exposed zebrafish parents changed substantially, but the disruption was not transferred to their respective offspring without exposure. However, the perturbation of insulin-related signaling pathways caused by TC exposure was not attenuated in the zebrafish offspring after removal of TC exposure. Taken together, our findings suggest that chronic exposure to TC disturbs gut microbial communities and metabolism and exerts chronic effects on the insulin/IGF-1 mediated signaling cascades, implying that exposure to antibiotics not only leads to the selection of resistant microbes but also poses long-term deleterious health risks for the next generation.