The Evaluation Framework of Spatially Patterned Effects of Carbon Nanoparticles on the Intestine of Mice.

Carbon nanoparticles have been widely applied in antimicrobial packaging and biomedicine owing to their unique physicochemical properties. Consequently, frequent oral exposure to carbon nanoparticles makes the intestine one of the primary targets of nanoparticle-induced toxicity. However, a systematic framework for evaluating nanoparticle-induced intestinal injury is still lacking. Here, we propose spatially patterned effects (SPE) as a comprehensive framework to describe ordered and compartment-specific biological responses following oral nanoparticle exposure. Our study demonstrates that exposure to single-walled carbon nanotubes (SWCNTs) or graphene oxide (GO) triggers a spatially ordered cascade of nano-mucus, nano-epithelial, nano-microbiota, and nano-immune interactions across distinct intestinal compartments. Both SWCNTs and GO directly disrupt mucus barrier integrity by interacting with mucin 2 (MUC2), which subsequently impairs epithelial homeostasis and thereby promotes bacterial translocation. These alterations are further accompanied by gut microbial dysbiosis, broad microbiota-associated metabolic remodeling, and activation of intestinal inflammatory responses. Collectively, the SPE framework provides a systematic perspective for understanding nano-intestine interactions and may facilitate the development of safer nanoparticles and more rational nanomedicine strategies for intestinal diseases.