The increasing use of chemicals requires a better understanding of their presence and dynamics in the environment, as well as their impact on ecosystems. The aim of this study was to validate the first steps of an innovative multi-omics approach based on metabolomics and 16S metabarcoding data for analyses of the fate and impact of contaminants in Mediterranean lagoons. Semi-targeted analytical procedures for water and sediment matrices were implemented to assess chemical contamination of the lagoon: forty-six compounds were detected, 28 of which could be quantified in water (between 0.09 and 47.4 ng/L) and sediment (between 0.008 and 26.3 ng/g) samples using the UHPLC-MS/MS instrument. In addition, a non-targeted approach (UHPLC-HRMS) using four different sample preparation protocols based on solid/liquid extractions or an automated pressurized fluid extraction system (EDGE^®) was carried out to determine the protocol with the best metabolome coverage, efficiency and reproducibility. Solid/liquid extraction using the solvent mixture acetonitrile/methanol (50/50) was evaluated as the best protocol. Microbial diversity in lagoon sediment was also measured after DNA extraction using five commercial extraction kits. Our study showed that the DNeasy PowerSoil Pro Qiagen kit (Promega, USA) was the most suitable for assessing microbial diversity in fresh sediment.

During recent decades, ultrasmall inorganic nanoparticles have attracted considerable interest due to their favorable biodistribution, pharmacokinetics and theranostic properties. In particular, AGuIX nanoparticles made of polysiloxane and gadolinium chelates were successfully translated to the clinics. In an aqueous medium, these nanoparticles are in dynamic equilibrium with polysiloxane fragments due to the hydrolysis of Si–O–Si bonds. Thanks to high-performance liquid chromatography coupled with electrospray ionization mass spectrometry, all these fragments were separated and identified.

The increasing use of chemicals requires a better understanding of their presence and their dynamics in the environment as well as their impact on ecosystems; it is therefore important to set up procedures. The aim of this study was to validate the first steps of an innovative multi-omics approach based on metabolomics and 16S metabarcoding data for future analyses of the contaminants fate and impact in Mediterranean lagoons. First, semi targeted analytical procedures for water and sediment matrices were set up to evaluate the lagoon contamination status. Forty-six compounds were detected, 28 could be quantified in both water (between 0.09 and 47.4 ng/L) and sediment (between 0.008 and 26.3 ng/g) samples using UHPLC-MS/MS instrument. Regarding the non-targeted metabolomics study (UHPLC-HRMS), four sample preparation protocols, based on solid/liquid extractions and an automated pressurized fluid extraction system (EDGE® extractions), were compared in terms of metabolome coverage, efficiency and reproducibility of the extraction methodology. A solid/liquid extraction using acetonitrile/methanol (50/50) solvent was the best protocol. On the other hand, in order to characterize the microbial diversity of the lagoon sediment using metabarcoding, five commercial kits for DNA extraction were evaluated. This study revealed that the DNeasy PowerSoil Pro Qiagen Kit (Promega, USA) was the best compromise for studies assessing microbial diversity in fresh sediment.

Background: Aryl phosphate esters (APEs), a main class of organophosphorus ester molecules, are widely used and commonly present in the environment. Health hazards associated with these compounds remain largely unknown and the effects of diphenyl phosphate (DPhP), one of their most frequent derivatives in human samples, are poorly characterised. Objective: Our aim was to investigate whether DPhP per se may represent a more relevant marker of exposure to APEs and determine its potential deleterious biological effects in chronically exposed mice. Methods: Conventional animals (FVB mice) were acutely (intravenous or oral gavage) or chronically (0.1 mg.mL ^-1 , 1 mg.mL ^-1 , 10 mg.mL ^-1 in drink water) exposed to relevant doses of DPhP or triphenyl phosphate (TPhP), one of its main precursors in the environment. Both molecules were measured in blood and other relevant tissues by liquid chromatography-mass spectrometry (LC-MS). Biological effects of chronic DPhP exposure were addressed through liver multi-omics analysis combining mRNA extraction and sequencing to high resolution LC-MS to determine the corresponding metabolic profile. Deep statistical exploration was performed to extract correlated information, guiding further physiological analyses (immunohistochemistry (IHC) and animal growth measurement). Results: Acute and chronic exposure to DPhP led to significant levels of this molecule in blood and other tissues, an effect missing with TPhP. Multi-omics analysis confirmed the existence of biological effects of DPhP, even at a very low dose of 0.1 mg.mL ^-1 in drinking water. Chemical structural homology and pathway mapping demonstrated a clear reduction of the fatty-acid catabolic processes centred on acylcarnitine and mitochondrial β-oxidation. Interestingly, mRNA expression confirmed and extended these observations by demonstrating at all tested doses the overall repression of genes involved in lipid catabolic processes and regulated by PPARα, a master regulator of β-oxidation and its associated ketogenesis. IHC analysis confirmed the alteration of these pathways by showing a specific downregulation of Hmgcs2, a kernel target gene of PPARα, at all doses tested, and surprisingly, a strong reduction of the lipid droplet content only at the highest dose. Overall, DPhP absorption led to weight loss, which was significant using the highest dose. Conclusions: Our results suggest that in mice, the effects of chronic exposure to DPhP, even at a low dose, are not negligible. Fatty acid metabolism in the liver in particular is essential for controlling fast and feast periods with adverse consequences on the overall physiology. Therefore, the impact of DPhP on circulating fat, cardiovascular and metabolic disease incidence deserves, in light of our results, further investigations.