Oral Feeding of Nanoplastics reduces Brain function of Mice by Inducing Intestinal IL-1β-producing Macrophages

Background and Aims Nanoplastics (NPs) as contaminants in food and water have drawn an increasing public attention. However, little is known about how NPs shape the gut immune landscape after entering the body. The objective of the study was to explore indirect effects caused by the interaction of NPs with the mammalian gut and whole immune system after entering the body. Methods In this study, we fabricated NPs (∼500 nm) and microplastics (MPs) (∼2 μm) and aimed to evaluate their in vivo effects by feeding them in mice. The mechanism was then investigated by various technology including single-cell RNA sequencing of gut and brain tissue. Results The results suggested that NPs showed a better ability to induce gut macrophage activation than did MPs. In addition, NPs triggered gut interleukin 1 beta (IL-1β)-producing macrophage reprogramming via inducing lysosomal damage after phagocytosis. More importantly, IL-1β released from the intestine could affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlated with a decline in cognitive and short-term memory in NPs-fed mice Conclusions Thus, this study provides new insight into the mechanism of action of the gut-brain axis and delineates the way NPs reduce brain function, highlights the importance to fix the plastic pollution problem worldwide. ### Competing Interest Statement The authors have declared no competing interest.