Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.
To reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis.
We assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.
Combining the results from the discovery and replication stages, we identified one causal bacterial genus, Bifidobacterium. A higher relative abundance of the Bifidobacterium genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339–1.922; P FDR = 4.19 × 10 −7] and CeD (OR: 1.401; 95% CI, 1.139–1.722; P FDR = 2.03 × 10 −3), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the Bifidobacterium genus.