Investigating Correlation Between Gut Microbiota and Rheumatoid Arthritis Subtypes by Mendelian Randomization

<b>Background</b>: Previous studies have demonstrated that the gut microbiota (GM) and rheumatoid arthritis (RA) are significantly associated, but the causal relationship has not been fully elucidated. <b>Methods</b>: We investigated the association between GM and RA using Mendelian randomization (MR) with two independent samples. Our study aimed to determine the causal relationship between gut microbiota and RA, including its seronegative and seropositive subtypes. Using data from a genome-wide association study (GWAS), we identified instrumental variables for 211 gut bacteria types. We then analyzed the FinnGen GWAS dataset, which included 3877 seronegative RA cases and 285,035 controls, along with 4290 seropositive RA cases and 368,362 controls, employing the inverse variance weighted (IVW) method and rigorous tests for pleiotropy and heterogeneity to ensure reliability. <b>Results</b>: The IVW results revealed that <i>Prevotella 9</i>, <i>Sutterella</i>, and <i>Christensenellaceae R.7</i> exhibited an adverse correlation with seronegative RA (<i>p</i> < 0.05). Additionally, <i>Lachnospira</i>, <i>Slackia</i>, <i>Roseburia</i>, <i>Barnesiella</i>, and <i>Prevotella 7</i> were associated with a reduced occurrence of seropositive RA (<i>p</i> < 0.05). Conversely, <i>Ruminococcaceae UCG002</i> and <i>Ruminococcus gauvreauii</i> were linked to an increased susceptibility to seropositive RA (<i>p</i> < 0.05). Notably, no significant heterogeneity (<i>p</i> > 0.05) or pleiotropy (<i>p</i> > 0.05) was detected in the analysis of the significant MR estimates. <b>Conclusions</b>: Our study suggested significant associations between several gut bacteria and RA subtypes, indicating a potential microbial influence on RA development. These findings enhance our understanding of the gut-joint axis in RA and highlight promising targets for future microbiota-based therapies.