Untargeted Metabolomics Reveals Antidepressant Effects in a Marine Photosynthetic Organism: The Diatom Phaeodactylum tricornutum as a Case Study

SIMPLE SUMMARY: Pharmaceutical compounds, designed to act specifically in human or animal organisms, may have unknown and undesirable effects on non-target organisms in the environment. Untargeted metabolomic analysis uncovered several common effects of fluoxetine in diatoms and mammal cells, specifically in shared metabolic pathways, revealing a common mode of action, including serotonin re-uptake, which is the molecular target of this antidepressant. Moreover, FT-ICR-based metabolomic profiling was shown to be a powerful tool for the identification of potential biomarkers of exposure in diatom cells, highlighting its value in the ecotoxicology of marine organisms. ABSTRACT: The increased use of antidepressants, along with their increased occurrence in aquatic environments, is of concern for marine organisms. Although these pharmaceutical compounds have been shown to negatively affect marine diatoms, their mode of action in these non-target, single-cell phototrophic organisms is yet unknown. Using a Fourier-transform ion cyclotron-resonance mass spectrometer (FT-ICR-MS) we evaluated the effects of fluoxetine in the metabolomics of the model diatom Phaeodactylum tricornutum, as well as the potential use of the identified metabolites as exposure biomarkers. Diatom growth was severely impaired after fluoxetine exposure, particularly in the highest dose tested, along with a down-regulation of photosynthetic and carbohydrate metabolisms. Notably, several mechanisms that are normally down-regulated by fluoxetine in mammal organisms were also down-regulated in diatoms (e.g., glycerolipid metabolism, phosphatidylinositol signalling pathway, vitamin metabolism, terpenoid backbone biosynthesis and serotonin remobilization metabolism). Additionally, the present work also identified a set of potential biomarkers of fluoxetine exposure that were up-regulated with increasing fluoxetine exposure concentration and are of high metabolic significance following the disclosed mode of action, reinforcing the use of metabolomics approaches in ecotoxicology.