Orally Administrated Engineered Probiotics to Enable Effective Uranium Exposure Protection

As a critical radionuclide in the nuclear fuel cycle, uranium if released to the environment during its mining, processing, and fuel disposal, or from depleted uranium weapons left in former war-zones, could accumulate in human bodies through oral uptake, posing high risks to the public health. In this study, probiotic Escherichia coli Nissle 1917 (EcN) genetically engineered to express a uranyl-binding protein (EcN-U) is developed to protect animals from oral uranium exposure. Leveraging its inherent intestinal colonizing ability, engineered EcN-U after oral administration could colonize in the animals' intestinal tracts and bind with uranyl in the drinking water, preventing uranyl from entering blood circulation and accelerating its clearance via feces. As the results, mice with acute oral exposure of high dose of uranyl if pretreated with EcN-U would survive from uranyl-induced death. As further demonstrated in mouse, rat and beagle dog models, animals with long-term oral exposure of uranyl if pretreated with EcN-U would show significantly reduced uranyl deposit in main organs, alleviated intestinal oxidative stress, normalized intestinal flora, as well as reduced tissue damages in other organs. Our work presents a general prevention strategy to efficiently and continuously protect the public against radioactive containments during nuclear accidents using orally fed natural probiotics.