Lacticaseibacillus paracasei Jlus66 ameliorates hyperuricemia by inhibiting xanthine oxidase activity, modulating uric acid transporter proteins and the gut microbiota.

A novel strain of Lacticaseibacillus paracasei Jlus66 was isolated from a traditional fermented dairy product known as "Nai Geda", and its role in hyperuricemia remains unclear. We constructed a mouse model using potassium oxonate (OXO) and a high-purine diet to examine the impacts of Jlus66 supplementation on hyperuricemia in vivo. The results revealed that Lacticaseibacillus paracasei Jlus66 intervention substantially lowered blood uric acid (UA) concentrations through suppressing xanthine oxidase (XOD) activity in the liver to reduce UA synthesis and modulating UA transport to enhance its renal excretion. Furthermore, Lacticaseibacillus paracasei Jlus66 supplementation increased short-chain fatty acids (SCFAs) in cecal samples, which might account for the reduced secretion of serum pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Lacticaseibacillus paracasei Jlus66 enhanced intestinal barrier function through upregulating tight junction proteins and reinstating gut microbiota homeostasis. In conclusion, Lacticaseibacillus paracasei Jlus66 may be a potential probiotic for the management of hyperuricemia through modulating gut microbiota, promoting UA excretion, and inhibiting UA synthesis.