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

Abstract

Background 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. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients. Methods Our 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. Results We 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. Conclusions The 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.

Gut Metagenome as a Potential Diagnostic and Predictive Biomarker in Slow Transit Constipation

“…Liu et al indicated that altered fecal microbiota might play vital roles in the pathogenesis of pediatric myasthenia gravis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric myasthenia gravis ( 34 ). Therefore, the intestinal microbiota in patients with STC may affect gut motility by altering host metabolism.…”

Big data analytics frameworks for the influence of gut microbiota on the development of tic disorder

“…Several studies have confirmed this mechanism, and reported elevated levels of pro-inflammatory cytokines [including IL-12 and TNF-α ( Leckman et al, 2005 )] and decreased levels of anti-inflammatory cytokines (including IL-13) in TD patients ( Parker-Athill et al, 2015 ). In addition, the decreased levels of Prevotella copri , Prevotella stercorea , and Roseburia faecis also determine short-chain fatty acid (SCFA) levels ( Louis et al, 2010 ; Liu et al, 2021 ). SCFAs play an anti-inflammatory and antimicrobial role in various interactions between gut microbiome and host metabolism ( Tan et al, 2014 ; Sanna et al, 2019 ).…”

GutMeta: online microbiome analysis and interactive visualization with build-in curated human gut microbiome database

“…The ‘classifier’ visualization displays six graphs the most common plots used in classifier construction and evaluation analysis [28, 33]. The first two graphs are the mean decrease accuracy and the mean decrease Gini of all participated species or genera in crossvalidation and sort in decreasing.…”

“…Users also could customized edit the colors, plot size, and label font size in the editor, and the changes will be applied to all the plots. Demo visualization is myasthenia gravis (MG) related samples from Liu et al [28]. (Fig.…”

“…Figure 4 Classifier visualizations of MG patients and healthy controls (HC)[28]. For feature selection, from right to left show mean decrease accuracy of features, mean decrease Gini of features, and number of features had been selected with cross-validation error.…”