Steering algal metabolic flux via EPS-mediated interfacial buffering for resilient pharmaceutical remediation in microplastic-polluted hotspots.

Microalgae-based natural attenuation is regarded as a low carbon alternative to traditional water treatments in decentralized water infrastructure. However, in its practical application for pharmaceuticals removal, it is often regulated by the ubiquitous microplastics (MPs) and algal extracellular polymeric substances (EPS), yet the underlying mechanisms remain poorly understood. Here, we investigated the differential responses of Euglena sp. to ibuprofen (IBU) and naproxen (NPX) under MP-EPS influence. Our results reveal that EPS servers as a critical regulator, which reversed IBU's growth inhibition while exacerbated NPX's toxicity in EPS-intact (EPS-C) treatments, highlighting that EPS dictates whether MP-pharmaceutical interactions shift between synergism and antagonism. Metabolomics uncovered pollutant-specific pathways, IBU removal with the efficiency increased from 58.9% to 79.7% in the presence of MPs was driven by algal metabolic reprogramming, specifically prioritizing the linoleic acid metabolism via the lipoxygenase pathway for active degradation. Conversely, NPX attenuation relied predominantly on passive adsorption (from 46.4% to 60.0% with MPs), with its toxicity triggering glycerophospholipid metabolism for membrane repair rather than metabolic breakdown. The remediator or victim status of the algal cell was determined by energy allocation. IBU induced stress triggered a compensatory metabolic shift, while NPX caused a carbon flux shift toward lipid repair, limiting energy availability for pollutant degradation. Furthermore, MPs (5 mg L-1) acted as auxiliary adsorbents alongside the EPS framework, synergistically enhancing pharmaceutical sequestration. These findings demonstrate that EPS-MP-algae interactions are not generic but constitute a structure-dependent biophysical-biochemical cascade, providing a new metabolic framework for assessing the ecological risks of co-contaminants in microalgae-based remediation.