The question of whether long-term chronic exposure to microplastics (MPs) could induce dose- and size-dependent adverse effects in mammals remains controversial and poorly understood. Our study explored potential health risks from dietary exposure to environmentally relevant doses of polystyrene (PS) MPs, through a mouse model and integrated analyses of the interruptions of fecal microbial metagenomes and plasma lipidomes. After 21 weeks of exposure to the MPs (40–100 μm), mice mainly exhibited gut microbiota dysbiosis, tissue inflammation, and plasma lipid metabolism disorder, although no notable accumulation of MPs was observed in the gut or liver. The change of the relative abundance of microbiota was strongly associated with the exposure dose and size of MPs while less significant effects were observed in gut damage and abnormal lipid metabolism. Moreover, multiomics data suggested that the host abnormal lipid metabolism was closely related to bowel function disruptions, including gut microbiota dysbiosis, increased gut permeability, and inflammation induced by MPs. We revealed for the first time that even without notable accumulation in mouse tissues, long-term exposure to MPs at environmentally relevant doses could still induce widespread health risks. This raises concern on the health risks from the exposure of humans and other mammals to environmentally relevant dose MPs.

The potential health risks of microplastics (MPs) to humans and other mammals have attracted global attention. However, whether long-term exposure to environmentally relevant doses of MPs could impair the reproductive functions of mammals and cause transgenerational effects on their offspring remains largely unclear. Our study revealed that long-term (i.e., 21 weeks) exposure to environmentally relevant doses of polystyrene MPs (40−100 μm) not only significantly decreased testicle relative weight but also decreased sperm quality (i.e., decreased sperm number and changed sperm phenotype), thus affecting the reproductive performance of male mice. The exposure also dysregulated lipid metabolism in their F1 offspring by altering 17 of 23 lipid classes. In particular, three lipid classes were closely related to nonalcoholic fatty liver disease; i.e., levels of alkylphosphatidylcholine, alkenylphosphatidylcholine, and alkenylphosphatidylethanolamine were significantly increased in the liver and plasma of F1 offspring. The lipid metabolism disruption also exhibited a dose-, gender-, and tissue-specific pattern. Our findings demonstrate for the first time the in vivo evidence of the male reproductive effects of exposure to environmentally relevant doses of MPs on terrestrial mammals and transgenerational effects on their offspring.

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Background: Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.Results: Male C57BL/6J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m³) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.Conclusion: These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.

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