植物乳杆菌CCFM8610对重金属镉的生物吸附机制及体内缓解镉毒性的作用机理

Cadmium (Cd) is a heavy metal which causes a broad range of adverse effects in humans. This non-essential metal is also classified as a human carcinogen. Cd exposure from environment and foods has become an important threat to food safety and human health. Our previous work had shown that a Lactobacillus plantarum CCFM8610 has the ability to alleviate Cd toxicity in mice, but the protective mechanism is not totally understood. Based on the results in the prophase, the objective of this study is to investigate the mechanisms of in vitro cadmium elimination and in vivo cadmium toxicity alleviation by Lactobacillus plantarum CCFM8610. The in vitro model of biosorption is established to study the Cd binding mechanism of Lactobacillus plantarum CCFM8610 with biochemical and genetical technology. Cell model is used to investigate the protective effects of lactobacillus plantarum CCFM8610 against Cd toxicity in cell. The protective mechanism is also evaluated in animal models with transcriptomic and metabolomic analysis, and the associated signal transduction pathways were studied. Differences of intestinal microflora between lactobacilli-treated mice and Cd-exposed mice are studied with metagenomic analysis to understand the restoration effects of Lactobacillus plantarum CCFM8610 on the damage of intestinal microecosystem induced by Cd exposure. Our study is aimed to explore a new function of probiotic lactobacilli for human health, and to develop a safe and efficacious nutritional supplement of diet to prevent and alleviate Cd toxicity.

镉是一种具有肝、肾等多靶器官毒性的重金属，被列为IA级致癌物。环境镉暴露已成为影响健康的重要风险因素。前期研究表明植物乳杆菌CCFM8610能缓解镉暴露导致的毒性效应，然而相关保护机制尚不清楚。基于此，本项目拟通过体外吸附、细胞和动物模型研究植物乳杆菌CCFM8610镉生物吸附和缓解镉毒性的作用机制。利用体外模型研究植物乳杆菌CCFM8610吸附镉的规律，在细胞和分子水平阐明植物乳杆菌CCFM8610吸附镉的机制；通过细胞和动物模型研究植物乳杆菌CCFM8610摄入在生理生化与代谢标志物指标上对镉毒性的缓解作用，利用转录组和代谢组分析方法揭示植物乳杆菌CCFM8610缓解镉毒性的作用机制及涉及的相关代谢通路；利用宏基因组分析技术研究镉暴露对肠道微生态的影响及植物乳杆菌CCFM8610对肠道微生态的重建。研究在乳酸菌功能挖掘方面形成关于乳酸菌干预镉毒性的新认识，为相关研究与应用提供理论依据.

镉暴露及镉中毒已成为严重的食品安全卫生问题，本项目选育得到具有生物减除镉功能的益生菌植物乳杆菌CCFM8610，通过吸附动力学及热力学分析分析确定植物乳杆菌对镉离子的吸附特性，利用组分剥离、蛋白质组学等手段从细胞生理及蛋白水平探索植物乳杆菌吸附镉离子的机制。同时利用HT-29肠细胞模型结合流式细胞术等技术研究植物乳杆菌对镉毒性的保护作用；利用小鼠、罗非鱼等动物模型研究植物乳杆菌在活体内降低镉含量、缓解镉诱导氧化应激及调节镉破坏肠道菌群的作用机制。项目的开展有助为针对镉中毒的膳食策略提供新的思路，同时为食品（如果蔬汁、大米等）中镉的减除提供新的微生物发酵策略。