Spatial multi-omics by high-resolution mass spectrometry for the comprehensive evaluation of emerging contaminants toxicity in freshwater sentinel species – SPECTRUM

Metabolic syndrome has led to an increased use of type 2 diabetes (T2D) medications, such as metformin, GLP-1 receptor agonists, and SGLT2 inhibitors. These medications have become environmental contaminants due to their presence in wastewater and drinking water. Their widespread occurrence and ecotoxicity raise concerns about their effects on aquatic ecosystems, particularly on sentinel species such as Gammarus fossarum, a freshwater crustacean. The European Union has implemented legislation, such as the Water Framework Directive and REACH, to monitor and regulate contaminants in aquatic systems. However, the complexity of environmental contamination requires the development of new tools to detect toxic exposure at the molecular level. The SPECTRUM project addresses this need by proposing a novel spatial multi-omics approach to study the effects of T2D medications on the amphipod G. fossarum. MALDI imaging, performed on a high-resolution mass spectrometer integrating isomer separation by ion mobility and a laser for post-ionization of molecules, will enable the identification of molecular biomarkers associated with exposure to these drugs (either alone or in mixtures). This unique and innovative approach will allow in situ analysis of a list of mRNAs, peptides (in situ protein digestion), metabolites, and lipids on the same tissue section, providing a detailed overview of the molecular changes induced by drug exposure in a highly integrative approach. We will also measure contaminants present in water and organisms using targeted mass spectrometry to build a comprehensive picture of exposure within a One Health framework. SPECTRUM will integrate spatial multi-omics data as well as exposure data to reveal molecular dysregulation in response to these drugs, thus contributing to a better understanding of the environmental effects of pharmaceutical pollution on sentinel species. The results will help inform regulatory strategies and, ultimately, improve the protection of freshwater ecosystems.