Designer probiotic-based living drugs for uric acid homeostasis control in hyperuricemic mice and rats.

Engineered probiotics can effectively manage hyperuricemia, a condition characterized by increased serum uric acid (UA) levels, leading to several chronic diseases. In this study, we design a probiotic-based UA level sensing and adjustment (PULSE)-engineered bacterium to maintain UA homeostasis. We generate a UA sensor in the E. coli Nissle 1917 strain based on a UA-responsive transcriptional repressor HucR, integrated with a synthetic promoter. Upon oral administration of engineered probiotics, PULSE cells dynamically regulate urate oxidase expression, reducing UA in the gastrointestinal tract in response to increased serum levels. We have demonstrated the potential of PULSE-engineered bacteria in maintaining UA balance in acute and chronic hyperuricemic mouse and rat models, highlighting the potential for long-term oral administration in reducing hyperuricemia-associated renal damage. Our probiotic-based living drug supports the progress of engineered probiotics as a safe, effective, and patient-friendly alternative to typical therapeutics for chronic disease management.