Cadmium-induced augmentation of fungal translocation promotes systemic infection in mice via gut barrier disruption and immune dysfunction

Abstract

Cadmium (Cd) disrupts the immune system and intestinal barrier, increasing infection risk and gut dysbiosis. Its impact on intestinal fungi, particularly the opportunistic pathogen Candida albicans, which can cause systemic infections in immunocompromised patients, is not well understood. Our study revealed that C. albicans exhibited high tolerance and maintained its morphogenetic switching in response to Cd. As C. albicans is not naturally found in the mouse gut, we attempted intestinal colonization of C. albicans-SC5314 strain using standard procedures. However, the intestinal fungal load decreased and was undetectable by 15th day. To assess the effects of sub-chronic Cd exposure, both oral and intravenous methods were used. Oral exposure to C. albicans (10⁵ CFU/ml) resulted in a 10-fold increase in intestinal translocation in Cd-exposed mice (0.98 mg/kg) compared to controls. Cd exposure also downregulated intestinal tight junction proteins and increased FITC-dextran permeability, indicating that Cd disrupts the intestinal barrier and facilitates C. albicans translocation. Moreover, Cd-exposed mice showed significant morbidity and higher fungal loads in organs after intravenous non-lethal dose of C. albicans, along with a subdued cytokine response. These findings highlight the significant impact of Cd on fungal pathogenicity and immune response, pointing to the broader health risks of Cd exposure.