Lacticaseibacillus rhamnosus NCUH061012 alleviates hyperuricemia via modulating gut microbiota and intestinal metabolites in mice

Hyperuricemia (HUA) has emerged as a public health burden. Recently, lactic acid bacteria (LAB) were reported to possess potential for alleviating HUA. However, LABs with anti-HUA potential are still scarce, considering which, as well as complex and unclear alleviating mechanisms, and it is worthy to find various LABs with antiHUA and investigate the alleviating mechanisms. In this study, Lacticaseibacillus rhamnosus NCUH061012 (LR012) with anti-HUA potential was obtained by isolating from infant feces, screening in vitro and evaluating in mice, and integrative fecal microbiome and metabolome were used for the first time to reveal the underlying mechanism of LAB in alleviating HUA. LR012 supplementation was effective in lowering the level of uric acid (UA), which prompted the decrease of serum uric acid (SUA) by 37.20% % compared with the HUA model group. LR012 facilitated the growth of Lactobacillus and Candidatus_Saccharimonas, and decreased the enrichment of Bacteroides, along with increasing short-chain fatty acids and decreasing lipopolysaccharide. Analysis of fecal metabolomics showed LR012 regulated more intestinal metabolites, including adenosine, hypoxanthine, xanthine, succinate, and tryptophan. Furthermore, these alterations in intestinal microbiota and metabolites showed positive associations with improving systemic inflammation and kidney damage, regulating UA production and excretion, and reducing SUA levels. It is deduced that the underlying mechanism of LR012 in alleviating HUA was to modulate intestinal microbiota and metabolites. In conclusion, LR012 was promising in preventing and alleviating HUA as a diet supplement, and these findings underscored the transformative potential of LR012 in alleviating HUA via intestinal remediation.