Intestinal barrier disruption by cadmium and microplastics: Mechanistic insights from integrated metabolomic and proteomic analysis in mice.

The continuous accumulation of cadmium (Cd) and microplastics (MPs) in the environment, coupled with their increasing usage and insufficient recycling measures, has increasingly severe impacts on human health, particularly by disrupting the integrity of the intestinal barrier. To investigate the mechanisms underlying intestinal damage in mice exposed to Cd and MPs simultaneously, we conducted a study involving 60 male Kunming mice, aged 8 weeks. The mice were randomly assigned to three groups: the control group (administered 0.2 mL of saline), the Cd group (administered 0.2 mL of 5 mg/kg CdCl2·2.5H2O), and the mixed exposure group (administered 0.2 mL of a mixture containing 5 mg/kg CdCl2·2.5H2O and 1 mg/d MPs). After euthanizing the mice at day 43 via cervical dislocation, we performed histopathological sections of colon tissue, proteomics analysis, metabolomics analysis, and multi-omics integrated analysis. Our findings demonstrate that co-exposure to Cd and MPs disrupts the expression levels of key molecules including glutamate (Glu), transcription factor SP1 (SP1), and ATP-binding cassette sub-family G member 2 (ABCG2). This perturbation alters metabolic pathways such as choline metabolism and central carbon metabolism, ultimately compromising intestinal barrier integrity and promoting cancer cell proliferation and invasion.