| Summary: | Gout is a form of prevalent and painful inflammatory arthritis characterized by elevated serum urate (SUA) levels. The gut microbiota (GM) is believed to influence the development of gout and SUA levels. Our study aimed to explore the causal relationship between GM composition and gout, as well as SUA levels, utilizing a two-sample Mendelian Randomization (MR) approach. A total of 196 GM taxa from five levels were available for analysis. We identified five taxa associated with SUA levels and 10 taxa associated with gout. In reverse MR analysis, we discovered that gout affected the composition of five GM taxa, while SUA levels influenced the composition of 30 GM taxa. Combining existing research, our study unveiled a potential negative feedback loop between phylum <i>Actinobacteria</i> and SUA levels, establishing connections with gout. We also proposed two novel associations connecting GM taxa (genus <i>Faecalibacterium</i> and genus <i>Prevotella9</i>), SUA levels, and gout. These findings provide compelling evidence of causal relationships between specific GM taxa with SUA levels and gout, contributing valuable insights for the treatment of gout.
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