Antipyretic pharmaceuticals intensify sewer H2S accumulation linked to biofilm matrix remodeling and altered sulfur metabolic potential.

Pharmaceuticals enter sewer systems before wastewater treatment, but their role in hazardous gas accumulation remains poorly understood. This study used long-term gravity sewer reactors to examine how acetaminophen (APAP) and ibuprofen (IBU) affect headspace hydrogen sulfide (H2S) accumulation, the properties of extracellular polymeric substances (EPS), and microbial functional potential in sewer biofilms. Both pharmaceuticals changed H2S from a stable baseline to a staged pattern with early suppression followed by accumulation above the control level. IBU showed earlier and higher H2S peaks than APAP, with the peak under 500 μg/L IBU exceeding that under 5000 μg/L APAP. Pharmaceutical exposure depleted extracellular proteins, enriched polysaccharides and humic acid, and promoted the retention of matrix-forming components in tightly bound EPS. QCM-D analysis showed marked decreases in |ΔD/ΔF| from 0.35 in the control to 0.03 and 0.09 under 5000 μg/L APAP and IBU exposure, respectively, indicating EPS interfacial rigidification. Metagenomic profiling further indicated reduced flagellar assembly, enhanced attachment-related potential, increased dsrA/B-associated terminal sulfite reduction potential, and reduced sulfide oxidation potential. These findings suggest that enhanced sewer H2S accumulation under antipyretic pharmaceutical exposure is associated with EPS interfacial rigidification and shifts in sulfur metabolic potential. These results identify antipyretic pharmaceuticals as underrecognized biofilm-structuring stressors associated with intensified sewer H2S accumulation and altered sulfur metabolic potential.