Abstract
BackgroundMyasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients.MethodsOur study recruited 53 pediatric MG patients and 46 age- and gender-matched healthy controls (HC). We sequenced the fecal samples of recruited individuals using whole-genome shotgun sequencing and analyzed the data with in-house bioinformatics pipeline.ResultsWe built an MG disease classifier based on the abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale. The classifier obtained 94% area under the curve (AUC) in cross-validation and 84% AUC in the independent validation cohort. Gut microbiome analysis revealed the presence of human adenovirus F/D in 10 MG patients. Significantly different pathways and gene families between MG patients and HC belonged to P. copri, Clostridium bartlettii, and Bacteroides massiliensis. Based on functional annotation, we found that the gut microbiome affects the production of short-chain fatty acids (SCFAs), and we confirmed the decrease in SCFA levels in pediatric MG patients via serum tests.ConclusionsThe study indicated that altered fecal microbiota might play vital roles in pediatric MG’s pathogenesis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric MG.
Highlights
Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue
We identified potential microbial marker species that could be used for MG identification by whole-genome shotgun sequencing analysis of fecal samples of pediatric MG patients and healthy controls (HC)
We found that the gut microbiome affects the production of short-chain fatty acids (SCFAs)
Summary
Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG It has not been determined whether the gut microbiota are altered in pediatric MG patients. Myasthenia gravis (MG) is a typical autoimmune disease that targets the neuromuscular junction by autoantibodies and is clinically manifested as skeletal muscle fatigue [1]. 80% of generalized MG cases and only 50% of patients with ocular MG have detectable antibodies against the acetylcholine receptor (AChR) [3, 4]. The diagnosis of pediatric MG can be challenging, because most children do not respond well to MG’s conventional diagnostic methods, such as fatigue test, repetitive nerve stimulation, and neostigmine test
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