Engineered probiotics for the in vivo mitigation of waterborne uranium toxicity and bioaccumulation

Uranium (U) contamination of water sources, arising from anthropogenic activities such as mining and nuclear fallout, poses a significant global threat to water quality and public health. Ingestion of U-contaminated water and food results in bioaccumulation, primarily within the kidneys and bones, leading to severe nephrotoxicity and potential long-term health consequences. Addressing this challenge, we present a novel bio-intervention strategy leveraging a genetically engineered probiotic for the prevention of U absorption at its primary entry point—the gastrointestinal tract. We engineered Escherichia coli Nissle 1917 (EcN) to express a high-affinity uranyl-binding protein (U09), generating the EcN-U strain. EcN-U sequestered soluble uranyl ions (UO 2 2+ ) within the gut lumen via selective and efficient binding, leading to fecal excretion and prevention of systemic absorption. In a murine model of acute UO 2 2+ exposure, EcN-U pre-treatment significantly enhanced survival rates. Furthermore, in chronic exposure models utilizing mice, rats, and beagle dogs, EcN-U pre-treatment demonstrably reduced U accumulation in target organs by approximately 80%. Concurrently, this intervention alleviated oxidative stress biomarkers, restored gut microbiota homeostasis, and mitigated intestinal histopathological damage. Our findings establish engineered probiotics as a pragmatic and potent strategy for environmental health protection, offering a proactive and viable solution for public health risk mitigation associated with waterborne uranium contamination.