Paediatric Myasthenia Gravis and Gut Microbiome

Shayan Ahmed, Jamia Millia Islamia, New Delhi

Paediatric Myasthenia gravis is an immune-mediated neuromuscular junction disorder characterized by periodic skeletal muscle weakening and lethargy. There are two forms of myasthenic weakness: ocular and generalized myasthenia gravis, based on whether the weakness is restricted to the ocular muscles. In Europe and North America, pediatric myasthenia gravis accounts for 10–15% of all Paediatric Myasthenia gravis cases. It is quite frequent in China, where up to 50% of individuals get the condition before the age of 15. Pediatric and adult myasthenia gravis have a lot of differences, these include symptoms, clinical severity, and antibody titer. The diagnosis of Paediatric Myasthenia gravis in children could be extremely challenging. This is due to the fact that most children do not respond well to myasthenia gravis conventional diagnostic techniques, which include the fatigue test, repetitive nerve stimulation, and neostigmine test.

The Microbial Markers for Diagnosis of Paediatric Myasthenia Gravis

Human Gut Microbiota act as Microbial Markers for Diagnosis of Pediatric Myasthenia Gravis. The human gastrointestinal tract is a complex ecosystem with a plethora of microorganisms living there. These microorganisms live in a symbiotic association with their hosts, and they affect human nutrition, metabolism, and immunological function. The influence of the gut microbiome on human health is becoming more evident each day and an imbalance in its makeup may lead to a variety of illnesses. Obesity, inflammatory bowel illness, and immunological disorders are among these diseases. 

Initially, microbiome sequencing approaches relied on amplicon sequencing of the 16S ribosomal RNA (rRNA) gene. However, a genome-wide association study (GWAS) based on whole-genome shotgun sequencing of the microbiome is currently suggested. This technique can identify the genomic composition of bacteria, archaea, fungi, and even viruses in the microbiome and assess its functional biological features at the species level.

According to recent research, the gut microbiota of myasthenia gravis patients differs from that of healthy persons. The clinical subgroups of myasthenia gravis are linked to differences in gut microbiota and faecal metabolites. On pediatric myasthenia gravis patients, whole-genome sequencing-based research was recently conducted. Short-chain fatty acids (SCFAs) are key metabolites generated by gut microbiota, and their quantity in faeces is considerably reduced in the adult myasthenia gravis group. The relation between the SCFAs and the gut microbiota of pediatric myasthenia gravis was investigated in this recent study. Potential microbial marker species were identified by the research team. These markers could be used to identify myasthenia gravis by whole-genome shotgun sequencing of faecal samples from pediatric myasthenia gravis patients and healthy controls. 

The research in discussion elucidates the fundamental roles and processes of gut microbiota in the development of pediatric myasthenia gravis. The new microbiota-targeted markers will aid in the diagnosis of pediatric myasthenia gravis considerably.

Outcomes of the Study

• Identification test used: The Wilcoxon differential test was used to identify species that had substantially different abundances in the myasthenia gravis and healthy control groups. 
• The abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale, was used to create a myasthenia gravis disease classifier. 
• In the independent validation cohort, the classifier achieved a 0.94 area under the curve in cross-validation and a 0.84 area under the curve. This validation showed that gut microbial characteristics may be utilized to differentiate myasthenia gravis patients from healthy controls. 
• The results also indicated differences in viral abundance between the myasthenia gravis and healthy controls groups, in addition to bacterial abundance. Human adenovirus D and human adenovirus F were found in the gut microbiota of pediatric patients, but no adenovirus was found in the healthy controls. 
• Viral infection has been postulated as a potential contributor in the early stages of myasthenia gravis.Other viruses that may be linked to myasthenia gravis include cytomegalovirus, human foamy virus, and Nile virus were also identified. 

It has been said that future studies on intestinal viruses could be of help in understanding the pathophysiology of pediatric myasthenia gravis.

• In the comparison of the myasthenia gravis and healthy controls cohorts, the MetaCyc annotation data revealed no statistical difference between unstratified pathways. 
• Short Chain Fatty Acids (SCFAs) have been shown to mediate a variety of interactions between the gut microbiota and host metabolism. Acetate, propionate, and butyrate are three molecules that make up more than 95 percent of the SCFAs in the human gut. In pediatric myasthenia gravis patients, SCFA analysis showed increased levels of butyric acid and isobutyric acid as compared to healthy controls. However, SCFA levels in the blood and the gut environment are not directly comparable. Testing for intestinal SCFAs would add to the evidence that altered intestinal flora has a role in the etiology of myasthenia gravis. 

The research in discussion holds significance in the fact that it demonstrates a novel method of understanding the etiology of pediatric myasthenia gravis, and generating new diagnostic and treatment tools for the disease. 

Also read: Effect of pollution on thyroxine levels in newborns

Source:Liu, P., Jiang, Y., Gu, S., Xue, Y., Yang, H., Li, Y., Wang, Y., Yan, C., Jia, P., Lin, X., & Qi, G. (2021). Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis. BMC medicine, 19(1), 159. https://doi.org/10.1186/s12916-021-02034-0 

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About the Author: Shayan Ahmed is currently pursuing a Master of Science degree in Microbiology from the Department of Biosciences, Jamia Millia Islamia, New Delhi. His area of research interest lies in antibiotic resistance and associated molecular mechanisms. His recent work was focused on understanding colistin resistance patterns in the environment, particularly in water bodies.