New insights into the inhibitory role of microplastics and heavy metals in antibiotic resistance dissemination within marine aquaculture systems

Microplastics (MPs) and heavy metals (HMs) commonly co-occur in marine aquaculture systems as emerging pollutants derived from feed inputs, antifouling coatings, and industrial effluents. Their accumulation can disturb microbial homeostasis and influence the dissemination of antibiotic resistance genes (ARGs). Contrary to the widely held view that these pollutants uniformly promote ARG transfer, recent evidence indicates that they may also suppress ARG propagation under specific conditions.Although MPs and HMs are often considered synergistic drivers of ARG transfer through oxidative stress and biofilm formation, reported effects vary with particle size, polymer aging, metal type, exposure duration, salinity, pH, dissolved organic matter (DOM), and experimental realism. Recent evidence indicates that MPs may also inhibit ARG propagation under high salinity, advanced aging, or near-neutral pH, when altered surface functional groups and metal complexation reduce metal bioavailability. To reconcile these divergent findings, this review proposes a threshold-dependent "counter-selection window" as a working hypothesis. This window is defined—based on a limited number of controlled laboratory and microcosm experiments—as an environmental range in which aged MPs with elevated surface O/C ratios (>0.2) and sustained ·OH radical generation form stable surface complexes with HM ions (e.g., Cu(II), Cr(VI)), thereby reducing the bioavailable metal pool and suppressing ARG horizontal transfer. Quantitative values cited in this review (e.g., pH 6–7, salinity >30‰, MP size 75–150 nm, and 21.4–42.3% HGT reduction) are drawn from these specific experimental systems and should not be interpreted as universal boundaries applicable to all marine aquaculture environments. The duration, spatial extent, and predictability of this window under diverse field conditions remain poorly constrained, and direct validation under realistic operational settings is urgently needed. We further emphasize that this inhibitory state is unstable: acidification or increased DOM may trigger metal desorption, collapse the counter-selection window, and restore ARG proliferation. However, we acknowledge that most mechanistic evidence is derived from laboratory pure-culture, freshwater, or soil studies; direct field data from marine aquaculture systems remain scarce. Therefore, the proposed counter-selection window and inhibitory effects should be interpreted as hypothesis-generating frameworks that require validation under realistic marine aquaculture conditions, considering salinity fluctuations, feed-derived organic matter, and hydrodynamic regimes. Moving beyond the conventional unidirectional co-selection narrative, this review critically evaluates the bidirectional regulation of ARG dynamics by MP–HM interactions as reported in laboratory and microcosm studies, integrates these mechanistic findings with consideration of marine aquaculture conditions, and identifies hypothesis-driven research priorities and management strategies for assessing and mitigating ecological risks associated with complex pollutant mixtures. We emphasize that all quantitative thresholds and the proposed ‘counter-selection window’ remain theoretical constructs until validated under realistic field conditions.