Differential Gut Microbiota and Fecal Metabolites Related With the Clinical Subtypes of Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Previous studies have observed that disturbances of gut microbiome may attribute to the development of MG through fecal metabolomic signatures in humans. However, whether there were differential gut microbial and fecal metabolomic phenotypes in different subtypes of MG remains unclear. Here, our objective was to explore whether the microbial and metabolic signatures of ocular (OMG) and generalized myasthenia gravis (GMG) were different, and further identify the shared and distinct markers for patients with OMG and GMG. In this study, 16S ribosomal RNA (rRNA) gene sequencing and gas chromatographymass spectrometry (GC/MS) were performed to capture the microbial and metabolic signatures of OMG and GMG, respectively. Random forest (RF) classifiers was used to identify the discriminative markers for OMG and GMG. Compared with healthy control (HC) group, GMG group, but not OMG group, showed a significant decrease in α-phylogenetic diversity. Both OMG and GMG groups, however, displayed significant gut microbial and metabolic disorders. Totally, we identified 20 OTUs and 9 metabolites specific to OMG group, and 23 OTUs and 7 metabolites specific to GMG group. Moreover, combinatorial biomarkers containing 15 discriminative OTUs and 2 differential metabolites were capable of discriminating OMG and GMG from each other, as well as from HCs, with AUC values ranging from 0.934 to 0.990. In conclusion, different subtypes of MG harbored differential gut microbiota, which generated discriminative fecal metabolism.

Gut Microbiota as Regulators of Th17/Treg Balance in Patients With Myasthenia Gravis

“…Based on a previous finding proposed by Tan et al. that different subtypes of MG have different microbiota composition patterns ( 72 ), we can speculate that fecal metabolites were different among different subtypes. Overall, all the above mentioned studies demonstrated the presence of dysregulated gut microbiota and microbial metabolites in patients with MG, thus providing a new entry point into the pathogenesis of MG and helping us understand the full picture of myasthenia gravis to propose new therapeutic strategies.…”

“…A study aimed to identify the distinctive gut microbes in different subtypes of MG showed that patients with GMG harbored lower community richness and diversity and more severe gut microbial disturbances than patients with OMG. Compared with HCs, the families of Bacteroidaceae and Veillonellaceae were significantly more abundant, whereas families of Lachnospiraceae, Erysipelotrichaceae, Ruminococcaceae, Peptostreptococcaceae, Coriobacteriaceae, and Clostridiaceae_1 were scarcer in patients with MG ( 72 ). According to published literature, previous studies have suggested that Veillonellaceae and Bacteroidales are positively correlated with certain autoimmune disorders, whereas Ruminococcaceae and Lachnospiraceae, the common short chain fatty acids (SCFAs) producers ( 73 ), are negatively correlated with these diseases ( 74 , 75 ).…”

Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis

“…This method can detect the microbiome’s genome composition at the species level of bacteria, archaea, fungi, and even viruses and analyze its functional biological characteristics [ 13 ]. Recent studies have reported that the gut microbiota in MG patients is altered compared to healthy people [ 14 , 15 ], and differential gut microbiota and fecal metabolites are related to the clinical subtypes of MG [ 16 ]. However, the studies are based on 16S research focusing on adult patients.…”

Oral Microbiota Profile in a Group of Anti-AChR Antibody–Positive Myasthenia Gravis Patients

“…MG is an autoimmune disease characterized by variable muscle weakness, with the primary subtype attributed to antibodies binding to AChR at the NMJ ( 5 , 11 , 12 ). Forkhead box (Fox) P3+ cluster of differentiation (CD) 4+ regulatory T cells (Tregs) play a critical role in maintaining self-tolerance and immune homeostasis to prevent the development of MG ( 12 ); these cells are depleted in MG patients, which may contribute to the pathogenesis of this disorder ( 13 , 14 ).…”