No alteration of gut microbiota in patients with myasthenia gravis compared to control patients: results from the MYBIOM trial

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disease, and gut microbiota have been considered a possible pathogenetic factor. Currently, studies have found differences in the gut microbiota of MG patients and healthy individuals. This study compared gut microbiota of MG patients to patients with non-inflammatory neurological disorders and to patients with other autoimmune disease of the peripheral nervous system in addition to healthy volunteers.Methods: Fecal samples of MG patients (n=41), control patients with non-inflammatory neurological disorders (n=18), patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n=6), and healthy volunteers (n=12) were collected, DNA was isolated, and the variable regions of the 16S rRNA gene were sequenced and statistically analyzed. Results: There was no differences in alpha- and beta-diversity displaying an unaltered bacterial diversity and structure of the microbial community between the MG group, the patients with non-inflammatory neurological disorders, and the CIDP group. Between the MG group and the healthy volunteers, alpha-diversity indices Shannon, Simpson, Chao 1 and ACE were significantly reduced. Within the fecal microbiota of MG patients, Deltaproteobacteria and Faecalibacterium were more abundant compared to controls with non-inflammatory diseases.Conclusions: Although the overall bacterial diversity and structure did not differ between the MG group compared to non-inflammatory and inflammatory neurological disorders, the significant difference in the abundance of Deltaproteobacteria and Faecalibacterium supports the considered role of gut microbiota as a possible contributor to MG pathogenesis. Further studies will be helpful to confirm these findings and to develop possible treatment strategies i.e. antibiotics.

背景：重症肌无力（Myasthenia Gravis, MG）是一种自身免疫性神经肌肉疾病，肠道菌群被认为是潜在的致病因素之一。目前已有研究证实，重症肌无力患者与健康个体的肠道菌群存在差异。本研究对比了重症肌无力患者、非炎症性神经系统疾病患者、周围神经系统其他自身免疫性疾病患者以及健康志愿者的肠道菌群特征。
方法：本研究共收集了41例重症肌无力患者、18例非炎症性神经系统疾病对照患者、6例慢性炎症性脱髓鞘性多发性神经根神经病（chronic inflammatory demyelinating polyradiculoneuropathy, CIDP）患者以及12例健康志愿者的粪便样本，提取样本DNA后对16S rRNA基因的可变区进行测序，并开展统计学分析。
结果：重症肌无力组、非炎症性神经系统疾病组以及CIDP组之间，α多样性与β多样性均无显著差异，提示三组的细菌多样性及微生物群落结构未发生改变。重症肌无力组与健康志愿者组相比，Shannon、Simpson、Chao 1及ACE等α多样性指数均显著降低。相较于非炎症性疾病对照组，重症肌无力患者的粪便菌群中，δ变形菌纲（Deltaproteobacteria）和粪杆菌属（Faecalibacterium）的丰度更高。
结论：尽管重症肌无力组与非炎症性、炎症性神经系统疾病组的整体细菌多样性及群落结构并无显著差异，但δ变形菌纲和粪杆菌属的丰度差异显著，这支持了肠道菌群作为重症肌无力潜在致病因素的假说。后续需开展更多研究以验证上述发现，并探索包括抗生素疗法在内的潜在治疗策略。