Chronic low-dose cadmium exposure disrupts gut microbiota and lipid metabolism to induce liver injury.

Cadmium (Cd) is a widespread environmental pollutant linked to liver injury and metabolic dysfunction, yet the gut-liver axis mechanisms remain unclear. We investigated chronic low-dose Cd exposure (100 nM CdCl2, 12 weeks) in mice using integrated metagenomic and metabolomic profiling. Despite intact intestinal morphology, Cd exposure induced hepatic inflammation, steatosis, and elevated transaminases. Shotgun metagenomics revealed gut microbiota shifts, with enrichment of Prevotella and depletion of Turicibacter. Fecal metabolomics showed disrupted bile acid detoxification and lipid remodeling. Functional analysis indicated upregulation of microbial fatty acid metabolism genes, suggesting compensatory but dysregulated responses. These findings demonstrate that chronic Cd exposure perturbs gut microbiota and metabolic outputs, driving liver injury via microbiota-mediated mechanisms. Our study highlights the gut-liver axis as a key target of Cd toxicity and points to microbiota-based interventions as potential therapies.