This study took Limosilactobacillus reuteri F22A089 as an example to explore domestication strategies to enhance its nucleoside degradation ability， which provided theoretical basis for obtaining strains with high uric acid lowering ability and targeted domestication of specific functions of probiotics. Two methods of in vitro and in vivo domestication were used to domesticate the ability of probiotics to degrade nucleosides. The results showed that the in vitro domestication method could not rapidly improve the nucleoside degradation ability of probiotics strains， and the nucleoside degradation ability of probiotics strains remained unchanged after 3 weeks of domestication. The study on in vivo domestication of probiotic strains by high-uric acid intestinal environment in mice driven by diet found that the domestication of Limosilactobacillus reuteri F22A089 increased the degradation ability of nucleoside， and the degradation rate of guanosine in some strains reached twice that of the original strain， indicating that it is feasible to target domestication of probiotic strains by host intestinal selection pressure. Whole genome and transcriptome sequencing and mutation site analysis were performed in domesticated strains. Three mutant genes (pbuG_1， rihB and yusV) related to uric acid lowering ability were noted. The mutations of these functional genes were closely related to the enhancement of uric acid lowering ability in domesticated strains. This study was the first to domesticate strains in vivo and improve their ability to degrade uric acid， providing a feasible domestication method for domesticating probiotics through the host gut and enhancing their probiotic efficacy.