Silent crisis in water: Navigating the labyrinth of antibiotic pollution and resistome spread for smart mitigation

The widespread contamination of antibiotics in aquatic ecosystems has precipitated a critical ecological dilemma: while indispensable for human health, their environmental dissemination accelerates antimicrobial resistance evolution. This comprehensive review delineates three interconnected environmental crises stemming from aquatic antibiotic pollution through evidence synthesis. First, antibiotics demonstrate “pseudo-persistence” through complex adsorption-desorption dynamics and transformation into stable, high-risk degradation products. Notably, ciprofloxacin transformation products exhibit substantially greater genotoxicity and significantly higher resistance gene induction compared to the parent compound, exacerbating ecological risks by interfering with microbial epigenetic regulation (including DNA methylation and non-coding RNA pathways). Second, antibiotic resistance genes (ARGs) transcend ecological boundaries via mobile genetic elements (MGEs), with certain integrative elements showing dramatically greater horizontal transfer efficiency than conventional plasmids. Environmentally adapted ARG variants infiltrate clinical environments through multiple transmission pathways, establishing a vicious cycle of resistance amplification. Confronting these crises requires advanced remediation strategies. To this end, advanced oxidation processes (AOPs) present promising potential, yet they face significant challenges for practical application, including matrix interference, substantial energy requirements, and the generation of hazardous byproducts that may themselves co-select for ARGs. To address these challenges, we propose an integrated “source-sink-effect-regulation” framework incorporating multi-omics approaches and computational toxicology. Future priorities include: (1) elucidating degradation product-epigenetics interactions, (2) quantifying cross-domain ARG flux via MGEs, (3) developing precision AOPs to minimize secondary risks, and (4) advancing integrated “One Health” governance. Resolving this crisis necessitates paradigm shifts from removal efficiency to risk precision and from terminal treatment to source prevention. • Reveals antibiotic “pseudo-persistence” & degradation products' epigenetic ARG regulation. • Quantifies ICEs as key MGEs driving cross-domain ARG spread, evolving high-risk variants. • Proposes “Exposure-Effect-Resistance” framework for prioritizing high-risk antibiotics/ARGs. • Addresses AOPs' toxic byproduct risks via biomimetic catalysts & AI-control for synergistic antibiotic/ARG removal.