The gut-joint axis: Genetic evidence for a causal association between gut microbiota and seropositive rheumatoid arthritis and seronegative rheumatoid arthritis

This study aimed to assess the causal relationship between GM and RA (seropositive RA and seronegative RA). A two-sample Mendelian randomization (MR) analysis was performed to assess the causality of GM on seropositive RA and seronegative RA. GM's genome-wide association study (GWAS) was used as the exposure, whereas the GWAS datasets of seropositive RA and seronegative RA were the outcomes. The primary analysis approach was used as inverse-variance weighted (IVW), followed by 3 additional MR methods (MR-Egger, weighted median, and weighted mode). Cochran's Q test was used to identify heterogeneity. The MR-Egger intercept test and leave-one-out analyses were used to assess horizontal pleiotropy. All statistical analyses were performed in R software. We discovered that Alloprevotella (IVW OR 0.84, 95% CI 0.71-0.99, P = .04) and Christensenellaceae R 7 group (IVW OR 0.71, 95% CI 0.52-0.99, P = .04) were negatively correlated with seropositive RA, Ruminococcaceae UCG002 (IVW OR 1.30, 95% CI 1.10-1.54, P = .002) was positively associated with seropositive RA. Actinomyces (IVW OR 0.73, 95% CI 0.54-0.99, P = .04), Christensenellaceae R 7 group (IVW OR 0.62, 95% CI 0.39-0.97, P = .04), Terrisporobacter (IVW OR 0.64, 95% CI 0.44-0.93, P = .02), Lactobacillales (IVW OR 0.65, 95% CI 0.47-0.90, P = .01) were negatively correlated with seronegative RA. The present MR analysis showed a protective effect of Alloprevotella and Christensenellaceae R 7 group and a potentially anti-protective effect of Ruminococcaceae UCG002 on seropositive RA; and a protective effect of Actinomyces, Christensenellaceae R 7 group, Terrisporobacter, and Lactobacillales on seronegative RA. Further experimental studies and randomized controlled trials are needed to validate these findings.