Tryptophan Metabolism-Regulating\nProbiotics Alleviate\nHyperuricemia by Protecting the Gut Barrier Integrity and Enhancing\nColonic Uric Acid Excretion

The balance of gut microbiota affects uric acid synthesis\nand excretion,\ninfluencing the development of hyperuricemia. This study aimed to\ninvestigate the effects and mechanisms of probiotics on hyperuricemia\nand adenine- and potassium oxonate-induced colonic damage. After two\nmonths of gavage at 10<sup>9</sup> CFU/day, the probiotic strains <i>Lactobacillus rhamnosus</i> UA260 and <i>Lactobacillus\nplantarum</i> YU28, identified through <i>in vitro</i> screening, significantly reduced serum uric acid levels in hyperuricemia\nmice from 109.71 ± 56.33 to 38.76 ± 15.06 and 33.22 ±\n6.91 μmol/L, respectively. These strains attenuated inflammatory,\nrepaired gut barrier damage, and enhanced colonic uric acid transporter\nfunction, thereby promoting uric acid excretion. Furthermore, the\nprobiotics significantly reshaped gut microbiota by increasing the\nabundance of beneficial bacteria, including <i>Lactobacillus</i> and <i>Coprococcus</i>, while modulating tryptophan, purine,\nand riboflavin metabolism. Changes in tryptophan metabolites, specifically\nindole-3-propionic acid and indole-3-acetic acid, were correlated\nwith xanthine oxidase activity, colonic injury, and the expression\nof the uric acid transporter protein ABCG2 during treatment. Probiotics\nintervention activated aryl hydrocarbon receptor pathways. These findings\nsuggest that probiotics alleviate hyperuricemia and colonic inflammatory\nby regulating gut microbiota composition and tryptophan microbial\nmetabolite pathways. Probiotics that modulate tryptophan microbial\nmetabolism may provide a potential strategy for treating or preventing\nhyperuricemia.