Association between gut microbiota and elevated serum urate in two independent cohorts.

OBJECTIVES Hyperuricemia is a precursor to gout and is often present in other metabolic diseases that are promoted by microbiome dysbiosis; however, no study has examined the association of gut microbiota with hyperuricemia and serum urate in humans. METHODS Study participants were derived from a community-based observational study, the Xiangya Osteoarthritis Study (discovery cohort). Hyperuricemia was defined as the presence of serum urate level >357 μmol/L for women and >416 μmol/L for men. Gut microbiota was analyzed using 16S rRNA sequencing from stool samples. We examined the relation of microbiota dysbiosis (i.e., richness, diversity, composition, and relative abundance of microbiota taxa) and predicted functional pathways to prevalent hyperuricemia and serum urate levels. We verified the associations in an independent observational study, the Step Study (validation cohort). RESULTS The discovery cohort consisted of 1,392 rural participants (mean age: 61.3 years; women: 57.4%; hyperuricemia: 17.2%). Participants with hyperuricemia had decreased richness and diversity, altered composition of microbiota, and lower relative abundances of genus Coprococcus compared with those with normouricemia. Predicted Kyoto Encyclopedia of Genes and Genomes metabolism pathways belonged to amino acid and nucleotide metabolisms were significantly altered in individuals with hyperuricemia compared with those with normouricemia. Gut microbiota richness, diversity and low relative abundances of genus Coprococcus were also associated with high levels of serum urate. These findings were replicated in the validation cohort with 480 participants. CONCLUSIONS Gut microbiota dysbiosis was associated with elevated serum urate levels. Our study raises the possibility that microbiota dysbiosis may modulate serum urate levels.