Mechanisms of levan in ameliorating hyperuricemia: Insight into levan on serum metabolites, gut microbiota, and function in hyperuricemia rats

Abstract

This study aims to investigate the effects of levan on the progression of hyperuricemia (HUA) rats and elucidate its underlying mechanisms. After levan intervention, both low and high-dose groups exhibited a significant decrease in serum uric acid (UA) levels, reaching 71.0 % and 77.5 %, respectively, compared to the model group. Furthermore, levan could alleviate renal pathological damage caused by glomerular cell vacuolation, inflammatory infiltration and collagen deposition. The results of enzyme activity assay and real-time fluorescence quantitative PCR showed that levan decreased UA production by inhibiting adenosine deaminase (ADA) activity and gene expression in liver; it upregulated ATP-binding cassette subfamily G member 2 protein (ABCG2) and organic anion transporter 1 (OAT1) transporter gene expression in the kidney, promoting UA excretion. Gut microbiome analysis indicated that levan regulated gut flora dysbiosis induced by HUA, resulting in up-regulated the abundance of beneficial bacteria (Muribaculaceae, Faecalibaculum, Bifidobacterium, and Lactobacillus) and decreased conditioned pathogenic bacteria (Escherichia_Shigella and Proteus). Non-targeted metabolomics showed changes in various serum metabolites associated with glycerophospholipid metabolism, lipid metabolism, and inflammation following oral administration of levan. Therefore, levan may be a promising functional dietary supplement for regulating the gut flora and remodeling of metabolic disorders in individuals with HUA.