Abstract:Lead is a common environmental and industrial toxin, which can cause persistent damage to the human nervous system, liver, and kidney. Finding effective mitigation strategies is one of the urgent issues to address. To evaluate the dose-effect of Lactiplantibacillus plantarum CCFM8661 on liver and kidney injury induced by heavy metal lead in mice, the changes of tissue physiological and biochemical indexes, microbial structure, and fecal metabolites in mice treated with different doses of L. plantarum CCFM8661 were investigated. The results showed that the heavy metal lead could significantly damage the liver, kidney, and other tissues of mice, mainly manifested as the significant reduction in enzyme activities of catalase (CAT) and glutathione (GSH), and the disturbance of gut microbiota and its metabolites composition. Oral administration of L. plantarum CCFM8661 significantly alleviated these changes induced by lead in mice, not only up-regulating the enzyme activities of CAT and GSH, but also alleviating the pathological indicators of liver and kidney, and significantly up-regulating the relative abundance of intestinal Lactobacillus and the content of isobutyric acid and other products. These results suggest that L. plantarum may play a role in alleviating lead poisoning by regulating gut microbiota and its metabolites. Notably, L. plantarum CCFM8661 showed a significant dose effect on the mitigation of lead injury, making it essential to determine the appropriate intake dose for the future application and promotion of L. plantarum CCFM8661.