Lactobacillus plantarum and quercetin synergistically ameliorate hyperuricemia through targeting multiple pathways

Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism, often accompanied by inflammation. It is characterized by an abnormal elevation in uric acid levels. In our investigation, the combined treatment with Lactobacillus plantarum DY1 and quercetin suppressed the activity of xanthine oxidase and adenosine deaminase, decreased the levels of uric acid, TNF-α and IL-β, downregulated gene expression of URAT1 and GLUT9, and upregulated OAT1 and ABCG2. The combination increased the abundance of Lactobacillus and decreased the abundance of norank_f_norank_o_Clostridia_UCG-014 and Roseburia. Metabolomics analysis revealed that the combination of probiotics and quercetin exhibited distinct metabolic pathways compared to their individual administrations. When compared to probiotics alone, the combination led to alterations in glutathione metabolism (oxidized glutathione and glutathione) as well as sphingolipid metabolism (sphingosine and sphinganine). When compared to quercetin alone, the combination resulted in variations in tryptophan metabolism (indole-3-acetamide, 5-hydroxy-L-tryptophan, indoleacetaldehyde, 3-(3-Indolyl)-2-oxopropanoic acid, 3-indoleacetic acid and 3-methylindole) along with purine metabolism (UA, xanthosine, cAMP, ADP and adenosine monophosphate). The subsequent fecal microbiota transplantation proved that the effect of the combination on reducing uric acid levels was mediated by the gut microbiota. Therefore, this new combination can be considered a promising adjuvant therapy capable of synergistically alleviating hyperuricemia.