Polystyrene nanoplastics promotes inflammation and aging in young mice through the oral-gut microbiome axis

With the escalating global pollution of nanoplastics, their impacts on organismal health have become a focal concern. The oral-gut microbiota axis plays a pivotal role in host health regulation, yet how nanoplastics influence this axis and drive inflammation and aging in young organisms remain undefined. This study aimed to investigate whether polystyrene nanoplastics (PS-NPs) promote inflammation and aging in young mice by disrupting the oral-gut microbiota axis. Therefore, we established a free-feeding model with 1000 μg/L PS-NPs using 8-week-old C57BL/6 mice. We quantified tissue inflammatory cytokines and cellular senescence markers to assess PS-NPs-induced inflammatory and aging effects, while 16S rRNA sequencing was employed to characterize oral and gut microbiota structural changes. We found that PS-NPs exposure significantly increased the expression levels of cellular senescence markers p21^Cip1/Waf and p16^Ink4a in lung and liver. Meanwhile, PS-NPs promoted the release of inflammatory cytokines such as IL-1β, IL-6 and TNF-α, by modulating the p38 MAPK pathway. In addition, PS-NPs also decreased the expression levels of antioxidant genes. Furthermore, 16S rRNA sequencing analysis revealed that PS-NPs exposure caused dysbiosis in oral and intestinal microbiota, manifested as significant alterations in microbial diversity and community structure. Our work provided mechanistic insights into nanoplastic toxicity and theoretical basis for developing preventive strategies.