Nanoplastics (NPs) can accumulate in the kidney and cause kidney injury, but the multi-organ interaction mechanism and preventive measures of kidney injury are still unclear. In this study, in vivo (60 μg/day, 42 days) and in vitro (0.4 μg/μL, 24 h) exposure models of polystyrene nanoplastics (PS-NPs, 80 nm) in mice and human kidney cortex proximal tubule epithelial cells (HK-2 cells) were established, respectively. Our study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice, which were related to lipid metabolism disorders mediated by intestinal flora. Desulfovibrionales-fatty acid synthase (Fasn)-docosahexaenoic acid (DHA) pathway may be one of the mechanisms of kidney injury in mice. Importantly, we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders (represented by DHA) and affects Fasn expression. In conclusion, our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.

Plastic pollution has become a non-negligible global pollution problem. Nanoplastics (NP) can reach the bone marrow with blood circulation and develop hematotoxicity, but potential mechanisms and prevention strategies are lacking. Here, we report the biological distribution of NP particles in the bone marrow of mice and hematopoietic toxicity after exposure to 60 µg of 80 nm NP for 42 days. NP exposure inhibited the capability of bone marrow hematopoietic stem cells to renew and differentiate. Notably, probiotics and melatonin supplementation significantly ameliorated NP-induced hematopoietic damage, and the former was superior to the latter. And interestingly, melatonin and probiotic interventions may involve different microbes and metabolites. After melatonin intervention, creatine showed a stronger correlation with NP-induced gut microbiota disorders. In contrast, probiotic intervention reversed the levels of more gut microbes and plasma metabolites. Of these, threonine, malonylcarnitine, and 3-hydroxybutyric acid might be potential performers in the regulation of hematopoietic toxicity by gut microbes, as they had a more significant relationship with the identified microbes. In conclusion, supplementation with melatonin or probiotics may be two candidates to prevent hematopoietic toxicity attributable to NP exposure. Also, the multi-omics results may lay the foundation for future investigations into in-depth mechanisms.