Because of its poor tolerance to bile salt, we decided to acclimatize DM9218 to bile salt. According to the industrial standard for the attenuation of LAB strains, we gradually acclimatized DM9218 from 0 to 0.3% bile salt containing media. After acclimation, the DM9218-A strain showed increased tolerance to 0.2% and 0.3% bile salt, while its purine degrading ability was not affected. The survival of DM9218-A in the GI tract of rats was determined by PCR-DGGE. The positive PCR-DGGE result provided evidence that DM9218-A successfully survived in the digestive tract of rats during the process of intragastric administration, as the DNA of dead bacteria is degraded by nucleases released in the GI tract. After the administration of DM9218 A stopped, the intestinal population of DM9218-A decreased, although it was still detectable. Moreover, DM9218-A treated rats displayed a microbial profile that was similar to untreated rats, which suggests that no perturbation of the host gut microbiota will be caused by intragastric administration of DM9218-A. It is currently unclear whether the intake of purine compounds can cause an elevation of serum uric acid. However, it has been difficult to establish an animal hyperuricemia model to test this, because commonly used laboratory animals such as rats, mice and rabbits, all express urate oxidase. This enzyme oxidizes the poorly soluble uric acid to water soluble allantoin, thus it is very difficult to induce hyperuricemia in these animals. As for humans and apes, mutation of the liver uricase gene resulted in inactivation of uric acid oxidase, therefore the occurrence of hyperuricemia in human is much higher than other mammalian. The methods of inducing hyperuricemia in rats include gene knockout, high purine diet, injection of potassium oxonate and the combination of high purine diet with potassium oxonate injection. The combination method can efficiently elevate serum uric acid in rats, and compared with potassium oxonate or high purine diet alone, the effect is greater and more stable and the duration of hyperuricemia longer. We therefore adopted this method to induce hyperuricemia in rats. After injection of potassium oxonate and high purine diet, the level of serum uric acid in treated rats was elevated more than 2.45 fold compared with controls. Application of DM9218-A to the hyperuricemic rats significantly decreased the uric acid level, but it was still higher than the allopurinol treated group. This is because allopurinol directly inhibits xanthine oxidase, a key enzyme in the purine metabolite pathway, which blocks the production of uric acid. In contrast, DM9218-A competes with the intestinal epithelium for the absorption of nucleosides in food. Therefore there are still free purine bases that can be absorbed by the epithelium and eventually metabolized into uric acid. The experimental results also suggest that, once applied to humans, the CUDC-907 HDAC inhibitor preventive effect of DM9218-A against hyperuricemia may be stronger than the effect of treatment after hyperuricemia has been induced. No significant differences in the level of serum creatinine and urea nitrogen were observed during the two week study period, which suggests that, because of the short modeling time, no serious renal injury has been induced in the rats.