Wastewater treatment attenuates ecological and human health resistome risk

Wastewater treatment is an important barrier to the environmental dissemination of antimicrobial resistance (AMR). However, its effectiveness is typically assessed using measures that do not directly capture resistance gene mobility or pathogen association. Here, we applied a configuration-based genomic risk framework (MetaCompare2.0) to 100 metagenomes (50 paired influent and effluent samples) collected from nine wastewater treatment works over 11 months, quantifying resistome risk based on associations between antimicrobial resistance genes (ARGs), mobile genetic elements, and host taxa. Influent samples exhibited highly variable ecological risk associated with mobile ARGs. Pathogen-associated human health risk was lower and more constrained. Wastewater treatment consistently reduced both ecological and human health risks, driving convergence towards uniformly lower risk resistome configurations. Risk attenuation was reproducible across treatment technologies and could not be explained by assembly quality or physicochemical variation. These findings indicate that wastewater treatment disrupts high-risk ARG configurations and highlight configuration-based genomic risk metrics as scalable tools for benchmarking environmental AMR mitigation.