Fluoxetine-Induced Changes in Escherichia coli Physiology: Effects of Secreted Metabolites on Cell Viability and Colistin Susceptibility

Fluoxetine has been increasingly recognized for its antimicrobial properties and potential to alter gut microbial composition and function. This study aimed to investigate the effects of fluoxetine exposure on Escherichia coli ATCC 25922, focusing on growth curve, protein secretion, metabolite-associated cytotoxicity, antibiotic interaction, and drug depletion. To assess potential impacts on bacterial physiology, E. coli was exposed to fluoxetine for 72 h. Bacterial growth and protein levels were measured. Supernatants were tested for cytotoxic effects on SW480 and HMC3 cell lines using MTT assay. Colistin susceptibility of Pseudomonas aeruginosa was evaluated in the presence of these supernatants to investigate the indirect modulation of antibiotic susceptibility. Fluoxetine exposure reduced bacterial growth while increasing extracellular protein levels. MIC values for colistin increased over time in both groups but showed no fluoxetine-specific differences. Although cytotoxicity testing specifically found reduced cell viability in fluoxetine-treated culture supernatants, no statistically significant difference was found compared to untreated controls. Finally, HPLC analysis demonstrated complete fluoxetine depletion from the bacterial culture by 72 h. These findings highlight potential microbiota-drug-host interactions and emphasize the need for mechanistic investigation of fluoxetine's effects on microbial physiology and host cell health.