Helicobacter pylori and arsenic co-exposure Intensify gastric barrier damage and serum metabolic disorder

Environmental arsenic exposure and Helicobacter pylori (H. pylori) infection are widespread public health concerns, yet their combined effects on gastric pathophysiology remain poorly understood. This study investigated the impact of H. pylori infection and arsenic co-exposure on gastric barrier integrity, oxidative stress, and serum metabolic profiles using a murine model. Mice were divided into control, single-exposure (arsenic), and multiple exposure group (H. pylori infection and arsenic exposure). Gastric barrier function was assessed via immunofluorescence staining of ZO-1 and occludin proteins. Untargeted metabolomics, including PCA, PLS-DA, and KEGG pathway enrichment analyses, were employed to characterize serum metabolic alterations. Gene expression levels of IL-18, Nrf2, Keap1, Cat, Sod1, and Hmox1 in gastric tissues were quantified by qRT-PCR, with Spearman correlation analysis to evaluate metabolite-gene expression relationships. Fluorescence intensity of ZO-1 and occludin was significantly reduced in H. pylori-infected mice, with further deterioration under arsenic co-exposure. Metabolomic profiling revealed distinct serum metabolic perturbations across groups, with the multiple exposure group exhibiting more pronounced fluctuations in metabolite levels (e.g., lipids, amino acids, and peptides) and greater pathway diversity compared to single exposure groups. qRT-PCR analysis demonstrated synergistic upregulation of oxidative stress (Nrf2, Hmox1) and inflammatory (IL-18) markers in the multiple exposure group. Spearman correlation analysis identified significant associations between specific metabolites (e.g., acylcarnitines, bile acids) and antioxidant gene expression, suggesting bidirectional interactions between systemic metabolism and gastric oxidative responses. This study establishes a murine model of H. pylori infection and arsenic co-exposure, revealing synergistic disruption of gastric barrier function, oxidative homeostasis, and metabolic regulation. These findings provide critical insights into the pathophysiological interplay between microbial infection and environmental toxicants, highlighting potential therapeutic targets for mitigating combined exposure risks.