The pharmaco-microbiomics of depression

ongoing

This interdisciplinary project aims to improve response to depression treatment using the gut microbiota. About one third of patients with depression do not respond to treatment with Selective-Serotonin-Reuptake-Inhibitors (SSRIs). Moreover, side effects such as gastrointestinal complaints are common. The commensal gut microbiota, residing in the human intestinal tract in trillions, likely contribute to variation in treatment efficacy. This makes them a promising candidate to improve treatment response. The highly inter-individual variable gut bacteria collectively represent an enormous amount of genes, enzymes and transporters (outnumbering human genes by 10-100 times). Hereby, the gut microbiota are involved in processing of orally ingested compounds, and, through the communication highway called the gut-brain-axis, interact with the central nervous system. Anti-depressant medication such as SSRIs reduce gut microbial diversity and change community dynamics. For example, in vitro studies have shown unintentional effects of SSRIs in the gut on a bacterium with a human-analogous serotonin transporter. This negatively affects serotonin metabolism in the gut, potentially contributing to side effects and reduced treatment response. Other similar mechanisms may occur, yet very limited experimental experimental data exist mapping which and how gut microbiota are impacted by SSRIs. Moreover, hardly any studies link SSRI medication induced gut microbial effects to treatment response. Using clinical cohorts, I will dissociate gut microbial profiles of patients responding versus not responding to their SSRI medication. In a culturing experiment, fecal material of such responders and non-responders will be characterized in terms of growth profile after SSRI exposure, transcriptomic and metabolomics. Using these results, a probiotics product will be developed. This project contains clinical, microbial and applied work with great societal and economic potential.