Beyond Co-Occurrence: A Framework for Interpreting Antibiotic-ARG Decoupling in Aquatic Systems and Its Implications for Aquatic Animal Health in a Changing World.

Antibiotics and antibiotic resistance genes (ARGs) are widespread in aquatic ecosystems affected by climate variability, urbanization, and intensifying aquaculture. Yet parent-antibiotic concentrations and resistance-related genetic endpoints do not always vary in parallel across seasons, sites, or environmental compartments. This discrepancy matters for aquatic animals as ecological receptors, potential vectors, and targets for antimicrobial resistance monitoring and management. To examine whether transport, retention, and biological processes may contribute to these mismatches, we conducted a structured narrative review. We screened studies retrieved from Web of Science Core Collection, Scopus, and PubMed for paired measurements in aquatic systems. Of 98 field studies, 25 provided sufficient paired data for matched chemical-genetic assessment. Among these, 16 provided Moderate evidence and 9 provided Suggestive evidence for coupled, mismatched, or compartment-dependent responses. No study met the stricter criteria for field-supported legacy persistence. Seasonal reversals, spatial divergence, and differences among water, particles, and sediments suggest that water-column antibiotic concentrations alone are incomplete proxies for ARG abundance. Such measurements alone cannot assess ARG mobility or host context. Potential contributors include sediment and biofilm retention, extracellular DNA, hydrodynamic redistribution, horizontal gene transfer, transformation products, and co-selective stressors, although their relative roles remain unresolved. These findings support monitoring that combines chemical and genetic endpoints with information on sources, hydrology, compartments, and hosts to inform aquatic-animal risk assessment and management.