Causal associations between gut microbiota and rheumatoid arthritis: A two-sample Mendelian randomization study

The gut microbiota has been implicated in the development of rheumatoid arthritis (RA), but whether these associations reflect causal relationships remains unclear. We conducted a two-sample Mendelian randomization analysis to investigate the potential causal effects of gut microbial taxa on RA risk. Summary-level data from the MiBioGen consortium (n = 13,266) and a large RA genome-wide association study (n = 97,173) were used. Multiple Mendelian randomization methods and sensitivity analyses were applied to ensure robustness. Four microbial taxa showed nominal associations with RA. Increased abundance of Catenibacterium, Desulfovibrio, and Ruminiclostridium 6 was associated with a higher risk of RA, while Lachnospiraceae (UCG008) appeared to have a protective effect. Although these associations did not meet Bonferroni-corrected significance, results were consistent across analytical methods with no evidence of pleiotropy or heterogeneity. This study provides genetic evidence supporting a potential causal link between specific gut microbes and RA risk. The findings highlight host immune modulation as a possible pathway connecting the gut microbiome to RA and identify candidate taxa for future mechanistic and therapeutic research.