Gut microbiota and Sjögren's syndrome: a two-sample Mendelian randomization study

Area of Science:

• Microbiome research
• Genetics
• Immunology

Background:

• The gut microbiota (GM) is increasingly recognized for its role in autoimmune diseases.
• Sjögren's Syndrome (SS) is an autoimmune disorder with a known association with GM, but causality remains unclear.

Approach:

• A two-sample Mendelian randomization study (TSMR) was conducted using the largest available genome-wide association study (GWAS) meta-analysis data from the MiBioGen consortium (n=13,266).
• Multiple statistical methods, including inverse variance weighted (IVW), MR-Egger, and MR-PRESSO, were employed to assess the causal relationship between GM and SS.
• Cochran's Q statistics were used to evaluate instrumental variable heterogeneity.

Key Points:

• Specific gut bacteria genera, including Fusicatenibacter and Ruminiclostridium9, showed a positive correlation with SS risk.
• Conversely, genera such as Porphyromonadaceae, Subdoligranulum, Butyricicoccus, and Lachnospiraceae were negatively correlated with SS risk.
• Four GM-related genes (ARAP3, NMUR1, TEC, SIRPD) were found to have a significant causal association with SS after FDR correction.

Conclusions:

• This study provides robust evidence for a causal relationship between gut microbiota composition and Sjögren's Syndrome risk.
• The findings suggest both protective and detrimental roles for specific gut bacteria and their associated genes in SS pathogenesis.
• Elucidating these genetic links offers novel therapeutic targets and research avenues for Sjögren's Syndrome.