Melatonin and Probiotics Ameliorate Nanoplastics-induced Hematopoietic Injury by Modulating the Gut Microbiota-metabolism

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.