Exposition à des nanoplastiques présents dans l'alimentation : devenir, transformations physico-chimiques et toxicité sur la sphère digestive

Plastic pollution is now one of the major environmental and health concerns. As a result of mechanical, chemical and/or biological fragmentation, plastic debris progressively break down into nanoplastics (NPLs, smaller than 1 µm). Over the past few years, several studies have reported the presence of NPLs in drinking water, as well as their release from food-contact packaging articles. These findings highlight ingestion as a primary route of human exposure. Consequently, the digestive system is one of the organs most likely to be affected first. However, the effects of NPLs on the gastrointestinal tract remain poorly understood, and most studies use commercially available NPLs that contain chemical substances (such as additives), which limits any toxicological interpretation. In this context, the present doctoral research was carried out in collaboration between Toxalim (Toulouse) and the Institute of Analytical Sciences and Physico-Chemistry for the Environment and Materials (Pau). The aim of this work was to investigate the fate and biological impact of fit-for-purpose polystyrene NPLs (PS-NPLs). These particles were synthesised without any chemical additives and could be traced within biological systems. The project adopted a multidisciplinary approach, combining physicochemical characterisation of the NPLs, models of simulated human gastrointestinal digestion and in vitro intestinal cell cultures, as well as an in vivo mouse model employed to explore responses along the gut-liver axis. In the animal study, adult male mice were subchronically exposed to gold-labelled PS-NPLs (0.1, 1 and 10 mg/kg body weight/day for 90 days). Interestingly, significant effects were observed at the lowest doses. These included increased body weight, impaired intestinal barrier with altered mucus quality, and changes in the gut microbiota. Importantly, these effects were diet-dependent (standard diet vs Western diet). Moreover, exposure to PS-NPLs exacerbated glucose intolerance in mice on a Western diet and promoted the accumulation of lipid droplets in the liver, with a shift towards larger droplet sizes. This hepatic effect occurred regardless of the dietary background.In parallel, two in vitro digestion models (static INFOGEST 2.0 and dynamic TIM-1) were used to compare two types of fluorescent PS-NPLs that differed in their degree of carboxylation (more or less aged). During the salivary phase, low-carboxylated NPLs adsorbed more α-amylase, thereby reducing its activity, compared to high-carboxylated NPLs. During the gastric phase, a pH-dependent aggregation of PS-NPL, as well as the formation of a protein corona, were observed in both protocols. Exposure of Caco-2/HT29-MTX co-cultures to digested or undigested PS-NPLs using the INFOGEST 2.0 protocol revealed no alteration to intestinal barrier integrity. In the undigested state, NPL translocation was dependent on the degree of PS-NPL carboxylation. Digestion enhanced the translocation of high-carboxylated NPLs and increased intracellular ATP production, suggesting the involvement of ATP-dependent internalisation pathways. Overall, this thesis demonstrates that PS-NPLs synthesised without chemical additives, when studied in particulate form, can induce both digestive and metabolic disturbances in mice, with pronounced effects even at low exposure doses. By combining in vivo and in vitro approaches, this work establishes links between the surface properties of NPLs, their physicochemical transformations during gastrointestinal digestion, their interactions with digestive enzymes, and the resulting biological responses. Taken together, these findings provide an integrated view of the behaviour and impact of PS-NPLs within the digestive system. They open translational perspectives towards the study of different at-risk populations and the implementation of environmental health policies, with the aim of better assessing the risks posed by NPLs to human health.