Charge-dependent effects of nanoplastics on Helicobacter pylori virulence and gastric pathogenesis.

Nanoplastics (NPs) are emerging environmental contaminants whose surface charge governs their biological interactions. This study investigated how differentially charged NPs modulate Helicobacter pylori virulence and gastric pathogenesis. A chronic infection mouse model was used to evaluate co-exposure to H. pylori and positive (PS-NH2), negative (PS-COOH), or neutral (PS) NPs. Gastric NPs accumulation and tissue injury were assessed by TEM and H&E staining. Oxidative stress markers, including reactive oxygen species (ROS) and malondialdehyde (MDA), antioxidants such as superoxide dismutase (SOD) and glutathione (GSH), and cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), the chemokine monocyte chemoattractant protein-1 (MCP-1), and the neutrophil enzyme myeloperoxidase (MPO), were quantified. The expression of virulence and adhesion genes, including cytotoxin-associated gene A (cagA), vacuolating cytotoxin A gene (vacA), blood group antigen-binding adhesin A gene (babA), and outer inflammatory protein A gene (oipA), was analyzed. Bacterial motility and biofilm formation were also evaluated. All NPs accumulated in gastric tissue and exacerbated injury, with severity following PS-NH2 > PS-COOH > PS. Co-exposure elevated oxidative stress and inflammation while reducing antioxidant capacity. Virulence and adhesion genes were upregulated across NPs groups, with PS-NH2 inducing early activation and PS-COOH causing sustained increases. PS-NH2 NPs showed no significant effect on early bacterial motility but suppressed late-stage swimming. Biofilm formation was markedly increased, particularly with PS-NH2 exposure. NPs exacerbate H. pylori-induced gastric injury in a surface charge-dependent manner by promoting bacterial virulence, oxidative stress, and inflammation. These findings provide new insights into host-pathogen interactions relevant to gastric disease.