Uric acid disequilibrium is implicated in chronic hyperuricemia-related diseases. Long-term monitoring and lowering of serum uric acid levels may be crucial for diagnosis and effective management of these conditions. However, current strategies are not sufficient for accurate diagnosis and successful long-term management of hyperuricemia. Moreover, drug-based therapeutics can cause side effects in patients. The intestinal tract plays an important role in maintaining healthy serum acid levels. Hence, we investigated the engineered human commensalEscherichia colias a novel method for diagnosis and long-term management of hyperuricemia. To monitor changes in uric acid concentration in the intestinal lumen, we developed a bioreporter using the uric acid responsive synthetic promoter,pucpro, and uric acid bindingBacillus subtilisPucR protein. Results demonstrated that the bioreporter module in commensalE. colican detect changes in uric acid concentration in a dose-dependent manner. To eliminate the excess uric acid, we designed a uric acid degradation module, which overexpresses anE. coliuric acid transporter and aB. subtilisurate oxidase. Strains engineered with this module degraded all the uric acid (250 µM) found in the environment within 24 h, which is significantly lower (p< 0.001) compared to wild typeE. coli. Finally, we designed anin vitromodel using human intestinal cell line, Caco-2, which provided a versatile tool to study the uric acid transport and degradation in an environment mimicking the human intestinal tract. Results showed that engineered commensalE. colireduced (p< 0.01) the apical uric acid concentration by 40.35% compared to wild typeE. coli. This study shows that reprogrammingE. coliholds promise as a valid alternative synthetic biology therapy to monitor and maintain healthy serum uric acid levels.