Effects And Mechanisms Of Lactobacillus Plantarum CCFM8610 Against Cadmium-induced Intestinal Injury

Cadmium(Cd)is a toxic metal occurring in the environment naturally.Owing to the industrial emissions and the agricultural application of Cd containing phosphate fertilizers and sewage sludge,Cd enters the food chain,which seriously endangers public health.Previous studies confirmed the ability of Lactobacillus plantarum CCFM8610 to against cadmium toxicity through cadmium adsorption and inflammation remission.However,studies were focused on livers and kidnies.While the effect and mechanism of Lactobacillus plantarum CCFM8610 against Cd-induced intestinal injury is still unclear.The aims of this study were to explore the effect and mechanism of Lactobacillus plantarum CCFM8610 in vitro and in vivo.Firstly,the effect of Lactobacillus plantarum CCFM8610 against Cd-induced intestinal injury was investigated by constructing the chronic cadmium exposure animal model.The results showed that Lactobacillus plantarum CCFM8610 can effectively reduce 20% cadmium accumulation in mice organs,accelerate the defecation rate which reduced the defecation time of cadmium-exposed mice by 2 hours,improve the water content of mice feces,and enhance the tension of mice colon muscle strips.The neurotransmitters(Nitric oxide,serotonin,substance P,acetylcholinesterase,vasoactive enteropeptide and calcitonin gene-related peptide)in the intestine were then detected.And immunolabeled the mice colon c-kit protein.The results showed that Lactobacillus plantarum CCFM8610 can regulate intestinal neurotransmitters,protect intestinal Cajal cells and protect intestinal motility after cadmium exposure.It is proved that the intestinal constipation induced by cadmium exposure can be effectively prevented by the intervention of Lactobacillus plantarum CCFM8610.Lactobacillus plantarum CCFM8610 can inhibit the relative expression of ERK,increase the relative expression of bcl-2,promote the anti-apoptotic activity of intestinal cells,and alleviate the intestinal stress and apoptosis in Cd-exposed mice intestine.In addition,Lactobacillus plantarum CCFM8610 significantly increased the relative expression of Claudin-1,DMT-1 and E-cadherin proteins in mice intestines and protected the intestinal barrier.16 s sequencing of mice intestinal flora shown that Lactobacillus plantarum CCFM8610 can regulate the intestinal microenvironment.It has been proved that Lactobacillus plantarum CCFM8610 can protect the intestinal barrier,inhibite intestinal inflammation and protect intestinal flora.Finally,proteomics was used to analysis the cadmium intestinal toxicity mechanism through Cd-exposed intestinal epithelial HT-29 cell.A total of 4,089 authentic proteins were detected through liquid chromatography-mass spectrometry and 168 differential proteins were screened.It was found that Cadmium can cause intracellular stress,increase the expression of Mitogen-activated protein kinase and NF-?B pathway-related proteins,and disturb the content of epithelial membrane protein.After the intervention of Lactobacillus plantarum CCFM8610 found that Cd-activated Ras-Raf-MEK-ERK and NF-?B signaling pathways can be inhibited,thereby alleviating intracellular stress and intracellular inflammation.Lactobacillus plantarum CCFM8610 was proved to reduce the relative expression of AKR1B10 in cadmium-exposed cells,and increase the relative expression of DDX21 and FLNA,thereby regulating intracellular energy metabolism,intracellular RNA and protein synthesis.Lactobacillus plantarum CCFM8610 can also protects the cell membrane proteins Claudin-1 and E-cadherin,thereby protecting the cell barrier.By comparison,it was also found that Lactobacillus plantarum CCFM8610 has certain strain specificity for relieving Cd-induced intestinal damages.