Tryptophan Metabolism-Regulating Probiotics Alleviate Hyperuricemia by Protecting the Gut Barrier Integrity and Enhancing Colonic Uric Acid Excretion

The balance of gut microbiota affects uric acid synthesis
and excretion,
influencing the development of hyperuricemia. This study aimed to
investigate the effects and mechanisms of probiotics on hyperuricemia
and adenine- and potassium oxonate-induced colonic damage. After two
months of gavage at 109 CFU/day, the probiotic strains Lactobacillus rhamnosus UA260 and Lactobacillus
plantarum YU28, identified through in vitro screening, significantly reduced serum uric acid levels in hyperuricemia
mice from 109.71 ± 56.33 to 38.76 ± 15.06 and 33.22 ±
6.91 μmol/L, respectively. These strains attenuated inflammatory,
repaired gut barrier damage, and enhanced colonic uric acid transporter
function, thereby promoting uric acid excretion. Furthermore, the
probiotics significantly reshaped gut microbiota by increasing the
abundance of beneficial bacteria, including Lactobacillus and Coprococcus, while modulating tryptophan, purine,
and riboflavin metabolism. Changes in tryptophan metabolites, specifically
indole-3-propionic acid and indole-3-acetic acid, were correlated
with xanthine oxidase activity, colonic injury, and the expression
of the uric acid transporter protein ABCG2 during treatment. Probiotics
intervention activated aryl hydrocarbon receptor pathways. These findings
suggest that probiotics alleviate hyperuricemia and colonic inflammatory
by regulating gut microbiota composition and tryptophan microbial
metabolite pathways. Probiotics that modulate tryptophan microbial
metabolism may provide a potential strategy for treating or preventing
hyperuricemia.