Gut microbiota and autoimmune neurologic disorders: a two-sample bidirectional Mendelian randomization study

Background: Increasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them has yet to be established.

Methods: From the published genome-wide association study (GWAS) summary statistics, we obtained data on the gut microbiota and three autoimmune neurologic disorders (Multiple Sclerosis, Guillain-Barré Syndrome, and Myasthenia Gravis). We then implemented a two-sample Mendelian Randomization (MR) to determine the causal relationship between the gut microbiota and the diseases. To validate the results, we conducted a series of sensitivity analyses. Finally, to verify the direction of causality, a reverse-causality analysis was done.

Results: We discovered that a higher relative abundance of the genus Ruminococcus2 (OR: 1.213, 95% CI: 1.006–1.462, p = 0.043, PFDR = 0.048) and the genus Roseburia (OR: 1.255, 95% CI: 1.012–1.556, p = 0.038, PFDR = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class Mollicutes (OR: 3.016, 95% CI: 1.228–7.411, p = 0.016, PFDR = 0.021), the genus Eubacterium (hallii group) (OR: 2.787, 95% CI: 1.140–6.816, p = 0.025, PFDR = 0.025), and the phylum Tenericutes (OR: 3.016, 95% CI: 1.228–7.411, p = 0.016, PFDR = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus Ruminococcaceae UCG005 (OR: 2.450, 95% CI: 1.072–5.598, p = 0.034, PFDR = 0.036), the genus Holdemania (OR: 2.437, 95% CI: 1.215–4.888, p = 0.012, PFDR = 0.024), genus Lachnoclostridium (OR: 3.681, 95% CI: 1.288–10.521, p = 0.015, PFDR = 0.025) and the genus Eubacterium (ruminantium group) (OR: 2.157, 95% CI: 1.211–3.843, p = 0.003, PFDR = 0.016) correlated with a greater chance of MG occurrence. No SNPs were identified as outliers through sensitivity analysis. Then, the results of the reverse MR analysis did not indicate any reverse causality.

Conclusion: Our findings demonstrate a causal relationship between the gut microbiota and three autoimmune neurologic disorders, providing novel insights into the mechanisms of these autoimmune neurologic disorders that are mediated by gut microbiota.