Association Between Gut Microbiota and Elevated Serum Urate in Two Independent Cohorts

OBJECTIVE: Hyperuricemia is a precursor to gout and is often present in other metabolic diseases that are promoted by microbiome dysbiosis. We undertook this study to examine the association of gut microbiota with hyperuricemia and serum urate levels 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 a serum urate level >357 μmoles/liter in women and >416 μmoles/liter in men. Gut microbiota were analyzed using 16S ribosomal RNA sequencing of stool samples. We examined the relationship 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 subjects from rural areas (mean age 61.3 years, 57.4% women, 17.2% with hyperuricemia). Participants with hyperuricemia had decreased richness and diversity, altered composition of microbiota, and lower relative abundances of genus Coprococcus compared to those with normouricemia. Predicted KEGG metabolism pathways including amino acid and nucleotide metabolisms were significantly altered in subjects with hyperuricemia compared to 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. CONCLUSION: Gut microbiota dysbiosis is associated with elevated serum urate levels. Our study examines the possibility that microbiota dysbiosis may modulate these levels.