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Emerging evidence has indicated an association between the gut microbiome and arthritis diseases including gout. This metagenomic study aims to investigate the possible role of gut microbiota in the development of gout. The results exhibit gout patients have higher abundance of Prevotella, Fusobacterium spp. and Bacteroides spp., whereas healthy controls have higher abundance of Enterobacteriaceae spp., butyrate-producing species, including Roseburia spp., Butyrivibrio spp. and Coprococcus spp. and anti-inflammatory Faecalibacterium prausnitzii. Functional analysis shows gut microbiome of gout patients have higher potential for fructose, mannose metabolism and lipid A biosynthesis, but lower potential for urate degradation and SCFAs production. Enterobacteriaceae spp. may contribute to urate degradation and provide immunostimulatory effect in healthy controls. A disease classifier based on gut microbiota shows positive performance in the discovery and validation cohorts (93.03% and 89.13% accuracy, respectively). The effect of uric-acid-lowering and anti-inflammatory drugs on the gut microbiome is mild. Integrative analyses of four additional diseases (obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis) indicates gout seems to be more similar to autoimmune diseases than metabolic diseases. This work demonstrates an altered gut microbiota might influence the development of gout and provides new insights into the diagnosis and treatment of the disease.

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