The gut-brain axis involved in polystyrene nanoplastics-induced neurotoxicity via reprogramming the circadian rhythm-related pathways.

The production of plastic is still increasing globally, which has led to an increasing number of plastic particles in the environment. Nanoplastics (NPs) can penetrate the blood-brain barrier and induce neurotoxicity, but in-depth mechanism and effective protection strategies are lacking. Here, C57BL/6 J mice were treated with 60 µg polystyrene NPs (PS-NPs, 80 nm) by intragastric administration for 42 days to establish NPs exposure model. We found that 80 nm PS-NPs could reach and cause neuronal damage in the hippocampus, and alter the expression of neuroplasticity-related molecules (5-HT, AChE, GABA, BDNF and CREB), and even affect the learning and memory ability of mice. Mechanistically, combined with the results of hippocampus transcriptome, gut microbiota 16 s ribosomal RNA and plasma metabolomics, we found that the gut-brain axis mediated circadian rhythm related pathways were involved in the neurotoxicity of NPs, especially Camk2g, Adcyap1 and Per1 may be the key genes. Both melatonin and probiotic can significantly reduce intestinal injury and restore the expression of circadian rhythm-related genes and neuroplasticity molecules, and the intervention effect of melatonin is more effective. Collectively, the results strongly suggest the gut-brain axis mediated hippocampal circadian rhythm changes involved in the neurotoxicity of PS-NPs. Melatonin or probiotics supplementation may have the application value in the prevention of neurotoxicity of PS-NPs.

Polystyrene micro-/nanoplastics induced hematopoietic damages via the crosstalk of gut microbiota, metabolites, and cytokines.

Micro-/nanoplastics (MNPLs), novel environmental pollutants, widely exist in the environment and life and bring health risks. Previous studies have shown that NMPLs can penetrate bone marrow, but whether they cause hematopoietic damage remains uncertain. In this study, C57BL/6J mice were treated with polystyrene MNPLs (PS-MNPLs, 10 µm, 5 µm and 80 nm) at 60 µg doses for 42 days by intragastric administration. We evaluated the hematopoietic toxicity induced by MNPLs and potential mechanisms via combining 16S rRNA, metabolomics, and cytokine chips. The results demonstrated that PS-MNPLs induced hematopoietic toxicity, which was manifested by the disorder of bone marrow cell arrangement, the reduction in colony-forming, self-renewal and differentiation capacity, and the increased proportion of lymphocytes. PS-MNPLs also disrupted the homeostasis of the gut microbiota, metabolism, and inflammation, all of which were correlated with hematotoxicity, suggesting that abnormal gut microbiota-metabolite-cytokine axes might be the crucial pathways in MNPLs-induced hematopoietic injury. In conclusion, our study systematically demonstrated that multi-scale PS-MNPLs induced hematopoietic toxicity via the crosstalk of gut microbiota, metabolites, and cytokines and provided valuable insights into MNPLs toxicity, which was conducive to health risk assessment and informed policy decisions regarding PS-MNPLs.