In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice

• Published in: The Science of the total environment 2024-06, Vol.927, p.172037-172037, Article 172037
• Main Authors: Zhang, Xianan, Wang, Jing, Liu, Yuansheng, Wang, Hemin, Li, Bin, Li, Qing, Wang, Yi, Zong, Yuru, Wang, Jiajia, Meng, Qingtao, Wu, Shenshen, Hao, Rongzhang, Li, Xiaobo, Chen, Rui, Chen, Hanqing
• Format: Article
• Language: English
• Subjects: Gut dysbiosis; Intestinal injury; Metabolic reprogramming; Polystyrene nanoplastics
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2024.172037

Despite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury. [Display omitted] •PS-NP exposure did not induce significant histopathological damage and intestinal epithelial dysfunction in mice.•Intestinal-accumulating PS-NPs drove the initiation of intestinal injury by disrupting the microstructure of enterocytes.•Intragastric PS-NPs induced gut microbiota dysbiosis accompanied by abnormal plasma metabolic fingerprinting.•PS-NPs exposure led to host-microbial spatial metabolic injury and ultimately initiated intestinal toxicity.