Causal Relationships Between the Oral Microbiome and Autoimmune Diseases: A Mendelian Randomization Study

The relationship between the oral microbiome and autoimmune diseases (ADs) has attracted considerable research interest. This study employed two-sample Mendelian randomization (MR) to investigate causal relationships between oral microbiota and six ADs, including rheumatoid arthritis (RA), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS). Using genome-wide association study data from oral microbiome features and ADs, we applied inverse-variance weighted estimation complemented by sensitivity analyses and reverse MR to assess robustness and reverse causation. Analysis of 309 tongue dorsum and 285 salivary microbial features identified four tongue dorsum and five salivary taxa with genome-wide significant causal effects. Specific microbial taxa from both oral niches demonstrated protective or risk-enhancing effects for RA, T1D, IBD, and MS, while no causal associations were found for SLE or SS. These findings establish the causal role of specific oral microbiota in autoimmune pathogenesis and highlight priority candidates for further investigation as potential microbial biomarkers.