Gut microbiota Lactobacillus johnsonii alleviates hyperuricemia by modulating intestinal urate and gut microbiota-derived butyrate.

Abstract

Background: Gut microbiota are important for uric acid (UA) metabolism within hyperuricemia (HUA); however, the underlying mechanisms of how the gut microbiota regulate intestinal UA metabolism remain unclear. This study aimed to explore the function of the intestine in HUA and to further reveal the possible mechanism.

Methods: We conducted gut microbiota depletion to validate the role of gut microbiota in UA metabolism. A mouse model of HUA was established, and the gut microbiota and microbiome-derived metabolites were analyzed via 16S RNA gene sequencing and metabolomics analysis. The mechanism of the gut microbiota in HUA was elucidated by in vivo and in vitro experiments.

Results: Antibiotic treatment elevated serum UA, disturbed purine metabolism, and decreased the relative abundance of Lactobacillus. HUA mice had a lower relative abundance of Lactobacillus johnsonii (L. johnsonii) and decreased gut butyrate concentration. Supplementation of L. johnsonii significantly reduces serum UA in hyperuricemia mice by preventing UA synthesis and promoting the excretion of gut purine metabolites. In addition, L. johnsonii enhanced intestinal UA excretion by heightening the urate transporter ABCG2 (adenosine triphosphate-binding cassette transporter, subfamily G, member 2) expression, and increasing the levels of butyrate, which upregulated ABCG2 expression via the Wnt5a/b/β-catenin signaling pathway.

Conclusion: Our results suggest that gut microbiota and microbiota-derived metabolites directly regulate gut UA metabolism, highlighting potential applications in the treatment of diet-induced HUA by targeting gut microbiota and its metabolites.