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May 17, 2026Medicine0 citationsOpen Access

Causal relationship between gut microbiota and rheumatoid arthritis: A bidirectional 2-sample Mendelian randomization study

Key Points

This study aims to evaluate the bidirectional causal relationship between gut microbiota and rheumatoid arthritis using Mendelian randomization.
Conducted forward and reverse Mendelian randomization analyses with gut microbiota and rheumatoid arthritis data.
Analyzed data from 6,959 gut microbiota samples and 6,236 rheumatoid arthritis cases.
Used inverse-variance-weighted methods and multiple sensitivity analyses for reliability.
Increased abundance of Bacilli, Eubacterium_F, and other microbiota types elevated rheumatoid arthritis risk (P IVW < .05).
Higher levels of Bifidobacterium breve and Oscillospirales were found protective against rheumatoid arthritis (P IVW < .05).
The reverse analysis linked rheumatoid arthritis to increased abundance of Blautia_A and Lachnospiraceae, with a significant association to many other microbiota types.

Abstract

To evaluate the bidirectional causal relationship between gut microbiota and Rheumatoid arthritis using Mendelian randomization (MR). Using gut microbiota data from the IEU OpenGWAS database (n = 5959, Finnish cohort) and rheumatoid arthritis genetic data from the Finnish database (6236 cases and 1, 47, 221 controls), forward and reverse MR analyses were conducted with gut microbiota and rheumatoid arthritis as exposure factors and outcomes, respectively. The significance threshold for forward MR was set at 1 × 10 −5, and the significance threshold for reverse MR analysis was set at 5 × 10 −8. The analysis primarily used inverse-variance-weighted (IVW) methods, supplemented by MR-Egger regression, weighted median methods, simple mode methods, and weighted mode methods. Sensitivity analyses were conducted to ensure the reliability of the results. The forward MR analysis indicated that increased abundances of Bacilli (CAG-345 sp000433315; P IVW =. 040), EubacteriumF sp000434115 (P IVW =. 031), Fimbriimonadia (P IVW =. 022), Christensenellales (GCA-900199385 sp900320755; P IVW =. 006), Muribaculaceae (P IVW =. 046), Lachnospira rogosae (P IVW =. 023), Leuconostoc (P IVW =. 025), Provencibacterium massiliense (P IVW =. 021), Provencibacterium (P IVW =. 039), and Rubneribacter sp002159915 (P IVW =. 016) elevated the risk of rheumatoid arthritis, while higher abundances of Actinobacteriota (P IVW =. 028), Bifidobacterium breve (P IVW =. 007), Bifidobacterium kashiwanohense (P IVW =. 009), Oscillospirales (CAG-448; P IVW =. 029), and Syntrophomonadia (P IVW =. 015) were protective against rheumatoid arthritis. The reverse MR analysis showed that rheumatoid arthritis was associated with increased abundances of 15 types of gut microbiota, including BlautiaA sp900066145 (P IVW =. 025), Lachnospiraceae (P IVW =. 041), Lactococcus lactis (P IVW =. 026), Terrisporobacter (P IVW =. 013), and Veillonella (P IVW =. 046), and decreased abundances of 17 types of gut microbiota, including Alistipes shahii (P IVW =. 032), Alistipes (P IVW =. 010), Barnesiellaceae (P IVW =. 008), Desulfovibrionaceae (P IVW =. 029), and Parabacteroides (P IVW =. 027). Cross-analysis did not reveal significant shared gut microbiota between forward and inverse MR analysis. Bidirectional sensitivity analysis validated the reliability of the study results. This study highlights the potential significance of specific gut microbiota in the pathogenesis of rheumatoid arthritis, providing new insights for the development of prevention, diagnosis, and therapeutic strategies for rheumatoid arthritis.

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