Mi Chuanhao, Hou Ajiao, Wang Ziyue, Qi Xianghua, Teng Jing
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Front Neurol. 2024 Jan 25;15:1309530. doi: 10.3389/fneur.2024.1309530. eCollection 2024.
Previous observational studies have provided cumulative data linking gut microbiota to myasthenia gravis (MG). However, the causal link between the two remains unexplored. Hence, the current study was performed to explore the causal link between them.
Mendelian randomization (MR) analysis was conducted using the summary statistics of 211 gut microbiota taxa and the largest genome-wide association studies (GWAS) for MG currently available. The inverse variance-weighted (IVW), MR-Egger, weighted median, and weighted mode methods were employed to ascertain the causal influence. Sensitivity studies utilizing several methodologies were then used to assess the robustness of the findings. Lastly, to evaluate reverse causality, a reverse MR analysis was performed.
Seven suggestive causal associations between the gastrointestinal microbiota and MG were identified based on the outcomes of the MR analysis. Specifically, phylum Actinobacteria (OR: 0.602, 95% CI: 0.405-0.896, = 0.012), class Gammaproteobacteria (OR: 0.587, 95% CI: 0.357-0.968, = 0.037), and families (OR: 0.695, 95% CI: 0.485-0.996, = 0.047), (OR: 0.614, 95% CI: 0.412-0.916, = 0.017), and (OR: 0.698, 95% CI: 0.505-0.964, = 0.029) had suggestive protective effects on MG, while order Mollicutes RF9 (OR: 1.424, 95% CI: 1.015-1.998, = 0.041) and genus (OR: 1.763, 95% CI: 1.220-2.547, = 0.003) were suggestive risk factors for MG. The outcomes indicate that neither heterogeneity nor horizontal pleiotropy had any discernible impact. Nevertheless, this reverse analysis did not reveal any apparent effect of MG on the gut microbiota composition.
The MR investigation has substantiated the suggestive causal connection between gut microbiota and MG, which may provide helpful insights for innovative therapeutic and preventative approaches for MG. Further randomized controlled trials are needed to elucidate the gut microbiota's precise role and therapeutic potential in the pathogenesis of MG.
先前的观察性研究已经提供了将肠道微生物群与重症肌无力（MG）联系起来的累积数据。然而，两者之间的因果关系仍未得到探索。因此，进行了本研究以探索它们之间的因果关系。
使用211种肠道微生物群分类群的汇总统计数据和目前可用的针对MG的最大全基因组关联研究（GWAS）进行孟德尔随机化（MR）分析。采用逆方差加权（IVW）、MR-Egger、加权中位数和加权模式方法来确定因果影响。然后利用几种方法进行敏感性研究，以评估研究结果的稳健性。最后，为了评估反向因果关系，进行了反向MR分析。
基于MR分析的结果，确定了肠道微生物群与MG之间的7种提示性因果关联。具体而言，放线菌门（OR：0.602，95%CI：0.405-0.896，P=0.012）、γ-变形菌纲（OR：0.587，95%CI：0.357-0.968，P=0.037）以及[具体科1]（OR：0.695，95%CI：0.485-0.996，P=0.047）、[具体科2]（OR：0.614，95%CI：0.412-0.916，P=0.017）和[具体科3]（OR：0.698,95%CI：0.505-0.964，P=0.029）对MG具有提示性保护作用，而柔膜菌纲RF9目（OR：1.424，95%CI：1.015-1.998，P=0.041）和[具体属]（OR：1.763，95%CI：1.220-2.547，P=0.003）是MG的提示性危险因素。结果表明，异质性和水平多效性均未产生任何明显影响。然而，这种反向分析并未揭示MG对肠道微生物群组成有任何明显影响。
MR研究证实了肠道微生物群与MG之间的提示性因果联系，这可能为MG的创新治疗和预防方法提供有益的见解。需要进一步的随机对照试验来阐明肠道微生物群在MG发病机制中的精确作用和治疗潜力。
