Potential causal associations of oral microbiome with rheumatoid arthritis, systemic lupus erythematosus and Sjögren’s disease

Abstract Background This study was to clarify potential bidirectional causal associations between oral microbiome and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren’s disease (SjD). Methods Two-sample Mendelian randomization (MR) analyses were conducted using summary statistics from genome-wide association study datasets for oral microbiota abundance, RA, SLE and SjD from European participants. Inverse-variance-weighted (IVW), MR-Egger, weighted median, and weighted mode methods were utilized. Multiple testing corrections were implemented using Bonferroni procedure. Results IVW method found that genetic predisposition of order Bacteroidales abundance in oral microbiome was significantly associated with a higher risk of RA (Odds ratio (OR) and 95% Confidence interval (95% CI): 1.04 (1.01, 1.08), P = 0.008, corrected P = 0.033). Furthermore, order Fusobacteriales abundance was positively associated with SLE but species Schaalia abundance was negatively associated with SLE by IVW method (OR and 95% CI: Fusobacteriales: 1.08 (1.01 − 1.17), P = 0.034, corrected P = 0.134; Schaalia: 0.87 (0.80 − 0.95), P = 0.003, corrected P = 0.058). Additionally, class Bacilli abundance in oral microbiome was related with a higher risk of SjD but family Pasteurellaceae in oral microbiome was related with a lower risk of SjD (IVW OR and 95% CI: Bacilli: 1.08 (1.01 − 1.15), P = 0.032, corrected P = 0.032; Pasteurellaceae: 0.94 (0.89 − 0.99), P = 0.037, corrected P = 0.184). Further MR-Egger, weighted median method and weighted mode method and sensitivity MR analyses after excluding confounding SNPs associated with smoking, periodontitis, and dental caries displayed similar trends. However, reverse MR analyses did not find significant associations of RA, SLE and SjD with oral microbiota abundance. Conclusion RA, SLE and SjD may be associated with specific oral bacteria abundance. Bacteroidales may be causally associated with RA. There was suggestive evidence for a positive association between Fusobacteriales and elevated SLE risk and an inverse association between Schaalia and reduced SLE risk. This MR analysis further identified a positive link between Bacilli and SjD but a possible negative link between Pasteurellaceae and SjD. The genetic evidence highlighted the important roles of oral microbiome in autoimmune diseases, although further studies were needed to validate these findings.