Causal Relationships Between Oral Microbiome And Autoimmune Diseases

This study aimed to investigate the causal relationship between the oral microbiome and six autoimmune diseases (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), by assessing the impact of genetic variations associated with the oral microbiome. We conducted two-sample Mendelian randomization (MR) analyses using oral microbiome genome-wide association studies (GWAS) data as exposures and GWAS data from six ADs as outcomes using the inverse-variance weighted (IVW) method. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, and MR-PRESSO, were performed to assess the robustness of the primary MR analyses findings. Additionally, reverse MR analysis was implemented to examine potential reverse causation. Among 309 tongue dorsum microbiomes (N = 2,017) and 285 salivary microbiomes (N = 1,915), our MR analyses found 4 tongue dorsum and 5 salivary bacterial genera were significantly associated with ADs. In tongue dorsum microbiomes, Eikenella was associated with a lower risk of RA, while Capnocytophaga, Veillonella, and Bacteroidaceae F0040 were associated with higher risks of T1D, IBD, and MS, respectively. In salivary microbiomes, Treponema showed a positive association with RA, while Capnocytophaga and Campylobacter were linked to T1D, and Gemella and Lachnoanaerobaculum to IBD. No significant causal associations were detected between the oral microbiome and either SLE or SS. Our findings highlight the significant role of the oral microbiome in autoimmune disease pathogenesis, suggesting its potential modulatory function in disease development.