Abstract
While the gluten-free diet (GFD) is primarily used to treat celiac disease (CD), recent research suggests it may also offer benefits for autoimmune-related diseases (ARDs), though findings remain inconsistent. This study aimed to investigate the potential protective effect of a GFD against ARDs by Mendelian Randomization (MR) analysis. Utilizing data from over 500,000 samples from the UK Biobank and other publicly available genome-wide association studies (GWAS), MR analysis revealed a significant negative causal relationship between GFD and the risk of developing rheumatoid arthritis (RA) (OR = 0.782, 95% CI = [0.727-0.841], p < 0.001). Mediation analysis identified immune cells such as CD14+ CD16+ monocyte absolute count (mediating 2.441% of the effect), CD14+ CD16+ monocyte percentage (2.346%), and CD20 on IgD+ CD38^dim B cells (3.119%) as potential mediators in the protective effect of GFD on RA. These findings suggest that GFD may help reduce RA risk by modulating specific immune cell populations. However, further research is necessary to clarify the exact mechanisms underlying these associations.