Antimicrobial activity of fluoxetine on the intestinal microbiota and its possible involvement in mental illness: an in vivo experimental study

Abstract

The microbiota–gut–brain axis (MGBA) has emerged as a critical element in understanding the pathophysiology of psychiatric disorders, highlighting the bidirectional communication between the gut microbiota and the central nervous system. Recent studies suggest that the gut microbiota may influence mental health through immunological, neuroendocrine, and metabolic pathways. This undergraduate thesis explores the interplay between fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and gut microbiota in the context of psychiatric illness, using an experimental animal model. The study aimed to evaluate the microbiological effects of chronic fluoxetine administration and assess its potential antimicrobial activity against specific gut bacterial strains. A total of 20 male Sprague-Dawley rats were divided into two groups: a control group and a fluoxetine-treated group receiving 10 mg/kg/day orally for 60 days. Fecal samples were analyzed to quantify changes in microbial populations. Additionally, minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of fluoxetine were determined for ten bacterial strains using standard microbiological techniques. Results showed a significant decrease in total bacterial counts in the fluoxetine group, particularly in beneficial genera such as Lactobacillus, Enterococcus, and coagulase-positive Staphylococcus, suggesting both direct and indirect antimicrobial effects. MIC and MBC analyses revealed variable susceptibility among bacterial species, with Ligilactobacillus murinus being the most sensitive strain. These findings support previous evidence that SSRIs, including fluoxetine, have antimicrobial properties that can disrupt gut microbial composition. The discussion highlights how these microbiota changes might influence neuroimmune pathways and potentially affect behavioral outcomes, emphasizing the MGBA’s role in psychiatric symptomatology. The work suggests that gut microbiota profiling could inform personalized psychiatric treatments and supports future therapeutic strategies involving psychobiotics or microbiota modulation. This study contributes to the growing body of research recognizing the gut microbiome as a dynamic player in mental health and calls for further integrative research combining microbiology, pharmacology, and behavioral neuroscience.