Causal relationship between gut microbiota and myasthenia gravis: a bidirectional mendelian randomization study

Area of Science:

• Microbiome research
• Immunology
• Genetics

Background:

• Observational studies suggest a link between gut microbiota and myasthenia gravis (MG).
• The causal relationship and protective mechanisms remain unclear.
• Investigating bidirectional causality is crucial for understanding MG pathogenesis.

Purpose of the Study:

• To determine the bidirectional causal relationship between gut microbiota and myasthenia gravis.
• To identify specific gut microbes influencing MG risk.
• To explore the role of gut microbiota in mitigating MG development.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis using large-scale datasets (MiBioGen and FinnGen).
• Bidirectional MR analysis to establish causality direction.
• Multiple MR methods (IVW, MR-Egger, weighted median) and pleiotropy/heterogeneity tests (Cochran's Q, MR-Egger intercept, MR-PRESSO).

Main Results:

• Forward MR identified a positive correlation between genus *Lachnoclostridium* and MG risk.
• Negative correlations were found for families *Clostridiaceae1*, *Defluviitaleaceae*, *Enterobacteriaceae*, and an unknown genus.
• Reverse MR indicated a negative correlation between MG risk and genus *Barnesiella*.

Conclusions:

• Evidence supports a bidirectional causal link between gut microbiota composition and myasthenia gravis.
• Specific microbial taxa are associated with MG risk, offering insights into disease mechanisms.
• Further basic and clinical research is needed to clarify the precise role and therapeutic potential of gut microbiota in MG.