The gut microbial diversity has been strongly associated with the occurrence of mood relating disorders including major depressive disorder (MDD). While the causality of this relationship is being investigated, the role of gut microbiota in the treatment of MDD has been somewhat overlooked. Currently, the dominant treatment for patients suffering from MDD is selective serotonin reuptake inhibitors (SSRIs), administered to ~10% of the global population albeit at very poor efficacy. In this presentation we provide a critical assessment of putative mechanisms by which physiologically relevant concentrations of SSRIs influence the gut microbiota and the implications that might have on mood disorders. First, an estimation of gut SSRI concentration is computed based on the pharmacokinetic properties of SSRIs and the temporal nature of their gastrointestinal transit. These concentrations are then used for an in vitro analysis of aerobic culturable gut microbes. The analysis reveals a significant change in microbial diversity and metabolic profile following SSRI supplementation. Analysis of individual isolates shows three types of response to the antidepressant: increased, reduced and unmodified growth rate. The antimicrobial mechanism of SSRIs is currently unknown however in silico analysis indicates that potential mechanisms might include inhibition of efflux pump or inhibition of amino acid transporters. Most importantly it is also unknown whether the antimicrobial effect of SSRIs serves to enhance or decrease efficacy of treatment. This raises important issues regarding the role that gut microbiota play in the treatment of mood related behaviours, which holds substantial potential clinical outcomes for patients suffering from MDD and other mood relating disorders.