New insights into the dose‐dependent inhibition of sludge fermentation by the antidepressant fluoxetine

Abstract Anaerobic sludge fermentation for short‐chain fatty acids (SCFAs) production is important for sludge reduction and resource recovery, but the effects of accumulating emerging contaminants such as the antidepressant fluoxetine (FLX) remain insufficiently understood. This work evaluates dose‐dependent impacts of FLX on SCFAs accumulation during alkaline anaerobic fermentation of excess sludge and explores the potential mechanisms. A clear concentration threshold was observed. No significant change occurred at ≤0.05 mg/kg volatile solids (VS), whereas SCFAs production decreased at >0.2 mg/kg VS. At 2.0 mg/kg VS, the cumulative SCFAs yield decreased to 136.5 mg/g VS, about 35% lower than the control. The inhibition was associated with reduced solubilization and hydrolysis, reflected by a decrease in maximum soluble chemical oxygen demand from 1941 to 1461 mg/L, suppression of key hydrolytic and acidogenic enzyme activities to ~80% of the control, and shifts in the fermentative microbiome with lower relative abundances of Firmicutes and Proteobacteria as well as acidogenic‐related genera including Lactococcus and Clostridium . These results clarify how FLX can constrain alkaline sludge fermentation and provide practical implications for maintaining stable SCFA recovery under pharmaceutical exposure.