Enrofloxacin (ENR) is widely used in animal husbandry, medical treatment and aquaculture, resulting in its discharge into various water environments. Although the toxicity effects of ENR on aquatic animal metabolism have been studied, there is still little information on the long‐term toxic hazard on the metabolism of cultured American shad. In this study, American shad juveniles were exposed to 0.1 mg/kg ENR for 10 months. The results showed that ENR could induce body weight gain in American shad. Alterations in metabolic pathways were found in pyrimidine metabolism, arginine and proline metabolism, the calcium signalling pathway and the arachidonic acid metabolism pathway. However, the alteration of neuroactive ligand–receptor interaction pathways was speculated to be related to weight gain through the regulation of the nervous system. The metabolomic and transcriptomic analysis suggested a similar pattern of pathway alterations. The multiomic data revealed that the specific metabolism alteration resulting from ENR exposure was associated with nutrition quality and predation ability in fish. Furthermore, previous works showed that ENR residues in fish tissue and the water environment would ultimately threaten human health and safety through food consumption. In sum, this study, for the first time, reveals that ENR exposure increases body weight in American shad and induces metabolic alteration. The ecotoxicity of antibiotic occurrences in indoor aquaculture systems should be further evaluated.
