Lead toxicity mitigation effect of a -chondroitin sulfate complex revealed by microbiome and metabolomic analyses.

Lead (Pb) is a highly toxic metal with no physiological function in humans, accumulates in the body through food intake, and causes gut microbiome disorders and other hazards. In the present study, we examined the efficacy of a combination of chondroitin sulfate and CCFM8661 (CCFM8661 + CS) on tissue Pb accumulation and pathological damage to the liver and kidneys, gut microbiota, and fecal metabolites in Pb-exposed mice. Oral administration of CCFM8661 + CS to Pb-exposed mice reduced Pb accumulation in the liver, kidney, and bone tissues (from 3.70, 14.11 and 121.20 mg g wet tissue to 2.26, 8.72 and 65.57 mg g wet tissue, respectively) and increased total antioxidant capacity, superoxide dismutase, and glutathione in the liver and kidneys. Additionally, gut microbiome analysis showed that CCFM8661 + CS intervention attenuated Pb-induced perturbation in gut microbiota, altering the abundance of bacteria such as , , , and . Untargeted metabolomics analyses showed that CCFM8661 + CS significantly increased cinnamoylglycine, hippuric acid, and equol (to 31.24, 28.77 and 20.13 times the baseline, respectively) and decreased guanine and 4-coumaric acid (0.30 and 0.09 times the baseline, respectively) in the feces, affecting pathways such as purine and amino acid metabolism. Further analyses showed that promoting Pb excretion and restoring the Pb-impaired gut microbiome and its metabolism may be important contributors to CCFM8661 + CS alleviation of Pb toxicity.