Plantago asiatica L. extract alleviates hyperuricemia-associated renal injury by modulating gut microbiota to inhibit NLRP3 inflammasome activation

Plantago asiatica L. (PTGA) is a widely used herbal medicine for the treatment of gout and hyperuricemia (HUA). Emerging evidence highlights the pivotal role of the gut microbiota in the pathogenesis of gout and HUA. However, existing research has failed to identify and verify the key mediator strains of PTGA that exert its role in lowering uric acid.

A hyperuricemia mouse model was established by intraperitoneal co-administration of hypoxanthine (100 mg/kg) combined with potassium oxonate (50 mg/kg) daily for 10 consecutive days. Serum uric acid (sUA) levels and renal function parameters were assessed using biochemical assay kits. 16S rRNA sequencing combined with non-targeted metabolomics was employed to characterize alterations in gut microbiota and intestinal metabolites. Western blotting was performed to examine the expression of intestinal and renal uric acid transporters, intestinal tight junction proteins, and NLRP3 inflammasome-related proteins. Finally, the mediate role of gut microbiota was verified through fecal microbiota transplantation (FMT) and oral supplementation with Lachnospiraceae bacterium.