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

Abstract

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.

The gut microbiota as a target to improve health conditions in a confined environment

“…This study shows, for the first time, that CEs significantly increase the UA content in urine, possibly as a result of abnormal metabolism. Studies have shown that UA is a biomarker of the oxidative stress state of the intestinal environment (Wang et al, 2022). Our results indicate that the intestine might be under oxidative stress in people in CEs.…”

“…The generation of intestinal ROS is related to physiological activities such as mood changes and insomnia (Brainard et al, 2016;Palinkas and Suedfeld, 2021). Studies have shown that intestinal cells secrete uric acid (UA) upon hydrogen peroxide stimulation to resist oxidative stress and that the increase in UA is related to imbalances in the gut microbiota (Wang et al, 2022). Some CE-simulation experiments show that light, gas, and work rhythms significantly affect the psychological states of the subjects, in turn affecting their cognitive abilities, teamwork, and other aspects of work efficiency (Berg et al, 2005;Kimhi, 2011).…”

Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout

“…Patients with HUA had reduced microbiota richness and diversity, an altered composition, and a lower relative abundance of Coprococcus than the normal controls ( Wei and Zhang, 2022 ). The probiotics Faecalibacterium , Gemmiger , Bacteroides , Roseburia , Bifidobacterium , and Akkermansia were significantly increased in asymptomatic HUA patients compared to the controls ( Yang et al., 2021 ).…”

The role of gut microbiota in gout: Is gut microbiota a potential target for gout treatment

“…Gout has higher relative abundances of Prevotella and Bacteroides while lower relative abundances of Enterobacteriaceae , which might cause uric acid degradation dysfunction and the buildup of uric acid in gout ( Chu et al., 2021 ). Additionally, the greater serum urate (SU) level was closely connected to the lower relative abundance of Faecalibacterium in hyperuricemia ( Wei et al., 2021 ).…”

“…A study through the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis revealed significant differences in amino acid metabolism (phenylalanine, tyrosine and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism, and phosphate and phosphonate metabolism) and nucleotide metabolism (purine metabolism) between hyperuricemia and healthy controls. The gut microbiota’s metabolic dysfunction may influence serum uric acid levels through its impact on host metabolites ( Wei et al., 2021 ). The production of SCFAs (concentrations of acetate, propionate, and butyrate) derived from the gut microbiota in mice positively correlates with the effectiveness of treating hyperuricemia.…”