Lacticaseibacillus rhamnosus alleviates hyperuricemia by restricting intestinal nucleoside absorption

Area of Science:

• Microbiology
• Metabolic Disorders
• Gastroenterology

Background:

• Hyperuricemia is an increasing metabolic disorder.
• Current treatments focus on urate excretion or degradation, neglecting upstream regulation.
• The role of gut microbiota in purine metabolism requires further exploration.

Purpose of the Study:

• To investigate a novel probiotic strain for hyperuricemia management.
• To elucidate the mechanism of action for urate reduction by the probiotic.
• To explore upstream regulation of purine metabolism via gut microbiota.

Main Methods:

• Isolation and identification of a nucleoside-degrading probiotic strain, Lacticaseibacillus rhamnosus (L. rhamnosus).
• Evaluation of the urate-lowering effect in a hyperuricemia rat model.
• Multi-omics analyses, Caco-2 cell assays, gene cloning, and enzymatic assays to determine the mechanism.

Main Results:

• L. rhamnosus significantly reduced serum urate levels in hyperuricemia rats.
• The probiotic acts independently of renal urate transporter expression.
• L. rhamnosus utilizes intracellular nucleoside hydrolases to convert nucleosides into poorly absorbed purine bases, limiting intestinal uptake and hepatic substrate supply for urate synthesis.

Conclusions:

• L. rhamnosus alleviates hyperuricemia through a novel substrate-restriction mechanism.
• This study provides new insights into microbiota-based interventions for purine metabolism disorders.
• The findings support the development of L. rhamnosus as a potential therapeutic agent for hyperuricemia.