AUTHOR=Zhang Mengyuan , Fang Jie , Zheng Chamou , Lin Qing , Zhang Jiawei 

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

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1337632

DOI=10.3389/fmicb.2024.1337632

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Background</title><p>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.</p></sec><sec id="sec2"><title>Methods</title><p>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.</p></sec><sec id="sec3"><title>Results</title><p>We discovered that a higher relative abundance of the genus <italic>Ruminococcus2</italic> (OR: 1.213, 95% CI: 1.006–1.462, <italic>p</italic> = 0.043, P<sub>FDR</sub> = 0.048) and the genus <italic>Roseburia</italic> (OR: 1.255, 95% CI: 1.012–1.556, <italic>p</italic> = 0.038, P<sub>FDR</sub> = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class <italic>Mollicutes</italic> (OR: 3.016, 95% CI: 1.228–7.411, <italic>p</italic> = 0.016, P<sub>FDR</sub> = 0.021), the genus <italic>Eubacterium (hallii group)</italic> (OR: 2.787, 95% CI: 1.140–6.816, <italic>p</italic> = 0.025, P<sub>FDR</sub> = 0.025), and the phylum <italic>Tenericutes</italic> (OR: 3.016, 95% CI: 1.228–7.411, <italic>p</italic> = 0.016, P<sub>FDR</sub> = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus <italic>Ruminococcaceae UCG005</italic> (OR: 2.450, 95% CI: 1.072–5.598, <italic>p</italic> = 0.034, P<sub>FDR</sub> = 0.036), the genus <italic>Holdemania</italic> (OR: 2.437, 95% CI: 1.215–4.888, <italic>p</italic> = 0.012, P<sub>FDR</sub> = 0.024), genus <italic>Lachnoclostridium</italic> (OR: 3.681, 95% CI: 1.288–10.521, <italic>p</italic> = 0.015, P<sub>FDR</sub> = 0.025) and the genus <italic>Eubacterium (ruminantium group)</italic> (OR: 2.157, 95% CI: 1.211–3.843, <italic>p</italic> = 0.003, P<sub>FDR</sub> = 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.</p></sec><sec id="sec4"><title>Conclusion</title><p>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.</p></sec>