Intestinal inflammation is associated with higher cadmium burden, potentially via compromised gut barriers: Evidence from NHANES and colitic mouse model.

Rapid industrialization increases the risks of intestinal disorders and heavy metal exposure. Although existing studies have demonstrated that cadmium (Cd) induces intestinal inflammation, whether inflammation is associated with higher Cd absorption remains unexplored. Using NHANES 2005-2010 data and a Cd-contaminated rice-fed colitic mouse model, we found a positive association between intestinal inflammation and blood Cd levels. Compared with healthy individuals in NHANES, those with bowel leakage symptoms had 21.4% higher blood Cd levels (95% CI: 8.72%, 35.4%), whereas those with inflammatory bowel disease had 63.6% higher blood Cd levels (95% CI: 32.9%, 101.5%). Liver and kidney Cd accumulation in colitic mice was 2.2-fold and 3.1-fold higher, respectively, than that in healthy mice, implying increased Cd bioavailability associated with intestinal inflammation. This increase in colitic mice was correlated with the impaired colonic mucus layer and tight junctions, and with increased intestinal permeability to Cd, as evidenced by significantly decreased fecal Cd excretion (from 20.7 μg to 16.9 μg, p < 0.01). This association was further supported by the finding that probiotic and prebiotic supplementation improved gut health and lowered Cd bioavailability. In colitic mice, probiotic and prebiotic supplementation improved intestinal barrier function and alleviated intestinal inflammation, consequently reduced liver and kidney Cd accumulation by 19.2-43.8% and 30.8-60.0%, alongside a 15.0-32.8% increase in fecal Cd excretion. This study emphasizes that individuals with intestinal inflammation face an elevated risk of Cd toxicity, and thus should be prioritized for heavy metal exposure protection.