Compared with healthy individuals, patients with gout were found to have a significantly unique gut microbiota associated with dysregulated host urate degradation and systemic inflammation, according to study results published in NPJ Biofilms and Microbiomes.
Given the growing evidence suggesting a link between the gut microbiome and arthritis, Chu and colleagues sought to investigate the taxonomic and functional signatures of the gout microbiome, its association with gout-related clinical parameters, response to therapeutic interventions, and identification of gout-specific microbiome signatures compared with the other autoimmune and metabolic disorders.
In the current large-scale metagenomic analysis, the researchers examined the gut microbiome of 307 fecal samples collected longitudinally from 102 patients with gout and 86 healthy individuals. The study group included 2 cohorts — the discovery cohort included 140 samples (77 patients with gout and 63 healthy individuals) at baseline and 70, 40, and 9 fecal samples collected longitudinally from patients with gout at week 2, 4, and 24 post-baseline, respectively; the validation cohort included 48 samples (25 patients with gout and 23 healthy individuals).
Results of the study showed decreased microbial diversity in patients with gout compared with healthy individuals in both the discovery and validation cohorts. Bacteroides, Prevotella, and Fusobacterium were enriched in patients with gout, whereas bacterium SS3/4, Enterobacteriaceae species, and several butyrate-producing species, such as Roseburia species, Coprococcus species, Eubacterium species, and F prausnitzii, were enriched in healthy individuals. The ratio of Bacteroidetes to Firmicutes was higher in patients with gout (P =.0098). A total of 110 genera and 223 species were significantly different in abundance between patients with gout and healthy individuals (false discovery rate [FDR], P <.05).
Metagenomic analysis among patients with gout showed an abundance for genes in mannose, fructose metabolism and lipid A synthesis and a deficit for genes in urate degradation and short-chain fatty acid production. Among patients with gout, a 3-pronged correlation analysis between microbial species, functions, and clinical parameters showed an association between low Enterobacteriaceae and reduced functional potentials in amino acid metabolism and environmental sensing, leading to increased serum uric acid and C-reactive protein levels. Treating gout with uric acid lowering drugs and anti-inflammatory medications partially restored the gut microbiome at 24 weeks. Overall, gout metagenomes were similar to autoimmune metagenomes than those of metabolic disorders.
Using a random forest model, the researchers constructed a disease classifier based on the microbial gene-level profile. Three genes (gene IDs: 15049 [exo-alpha-sialidase], 415936 [N-6 DNA methylase], and 1697136 [relaxase/mobilization nuclease domain-containing protein]) were significantly enriched in patients with gout in the discovery cohort (area under the operating curve [AUC], 0.91), and 2 of the genes (15049 and 415936) showed an increasing trend in the validation cohort (AUC, 0.80).
Study limitations included the small sample size and limited generalizability of the findings to patients with gout.
The researchers concluded, “Our results showed a dysbiosis of gut microbiome in gout that was associated with increased SUA and systemic inflammation and may be partially restored by uric-acid-lowering and anti-inflammatory drug interventions over time.”
Chu Y, Sun S, Huang Y, et al. Metagenomic analysis revealed the potential role of gut microbiome in gout. NPJ Biofilms Microbiomes. 2021;7(1):66. doi:10.1038/s41522-021-00235-2