Reducing cadmium bioavailability in soil with micronutrient sulfates: Insights from duodenal transporter expression and intestinal microbiota in a mouse model.

Micronutrient sulfates have the potential to mitigate cadmium (Cd) accumulation in crops; however, their effects on soil Cd bioavailability remain unclear. To address this knowledge gap, mice were fed a diet containing 10% (w/w) amended Cd-contaminated calcareous soil (amendments: MnSO4, ZnSO4, FeSO4, or Na2SO4) for 14 days. Cd bioavailability was then assessed by measuring Cd accumulation in the kidney and liver (primary endpoints), duodenal transporter expression, fecal microbiota composition, and soil properties. The results demonstrated that all micronutrient sulfate treatments increased the acid-extractable fraction of Cd in soil. Concurrently, soil-available Mn and Zn increased by 94.79% and 89.31%, respectively, following their corresponding sulfate amendments, and available sulfur rose by 0.90- to 21.32-fold across all treatments. Compared with the control, Cd concentrations in the kidney and liver of mice treated with Mn, Zn, Fe, or Na sulfates significantly decreased by 25.95-35.36% and 20.75-35.30%, respectively, and Cd relative bioavailability (Cd-RBA) declined by 27.02-34.13% (p < 0.05). Significant negative correlations were observed between Cd-RBA and molar ratios of nMn/nCd, nFe/nCd, and nZn/nCd in the soil and mouse tissues. Further analyses identified a three-part protective mechanism: (1) Intestinal antagonism: downregulation of duodenal ZIP8 expression by Mn, Zn, and Fe treatments (by 66.49-88.30%), thereby limiting Cd uptake; (2) Microbiome restoration: significant reduction of the Firmicutes/Bacteroidota (F/B) ratio compared with the control group, with reductions of 6.02% (Mn), 15.53% (Zn), 51.11% (Fe), and 17.75% (Na); (3) Enterohepatic elimination: enhanced formation of Cd-S complexes and the resulting increase in fecal Cd excretion across all treatments (by 39.05-60.77%). In conclusion, micronutrient sulfate amendments mitigate Cd bioavailability through a concerted mechanism, involving soil chemical modification, luminal complexation, physiological antagonism, modulation of transporter gene expression, and microbiome-mediated enteric elimination.