Evidence for genetic causal relationships between gut microbiome, metabolites, and myasthenia gravis: a bidirectional Mendelian randomization study.

Background: Myasthenia gravis (MG) is an autoimmune disease observed to have connections with gut microbiome. We aimed to systematically assess the causal relationships between gut microbiome, gut microbiome-derived metabolites, and MG using Mendelian randomization (MR) approach. Methods: Summary-level genetic datasets from large-scale genome-wide association studies regarding 196 gut microbial taxa from the MiBioGen consortium (n=18,340), 72 derived metabolites from the TwinsUK and KORA studies (n=7,824), and antiacetylcholine receptor (AChR) antibody-positive MG (case=1,873, control=36,370) were employed for MR causal estimates. The inverse-variance weighted (IVW) method was utilized as the main analysis with MR-Egger, maximum likelihood, simple mode, and weighted median as complements. The tests of Cochran's Q, MR-Egger intercept, Steiger, MR-PRESSO and leave-one-out were implemented for sensitivity analyses. Results: The forward MR estimates of IVW revealed significant causal associations of the abundance of phylum Actinobacteria, class Gammaproteobacteria, family Defluviitaleac, family Family XIII, and family Peptococcaceae with a reduced risk of MG. Conversely, the abundance of phylum Lentisphaerae, order Mollicutes RF9, order Victivallales, and genus Faecalibacterium was causally associated with an increased risk of MG. The reversed MR analysis proved negative causal correlations between the MG and the abundance of family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum. Regarding the derived metabolites, the IVW estimates revealed that elevated levels of beta-hydroxyisovalerate and methionine were causally associated with a decreased risk of MG, while increased levels of choline and kynurenine were linked to an increased risk of MG. Furthermore, genetically predicted MG was associated with a decreased level of cholesterol. The results obtained from complementary MR methods were similar. These findings remained robust in all sensitivity analyses. Conclusion: Our MR findings support the causal effects of specific gut microbiome taxa and derived metabolites on AChR antibody-positive MG, and vice versa, yielding novel insights into prevention and therapy targets of MG. Future studies may be warranted for validation and pursuing the precise mechanisms.

Myasthenia gravis: The pharmacological basis of traditional Chinese medicine for its clinical application.

We aimed to investigate the target and signal pathway of Smilacis Glabrae Rhixoma (SGR) in the treatment of myasthenia gravis (MG) based on network pharmacology, and to explore its potential molecular mechanism. The main active components of SGR were searched in the pharmacology database of traditional Chinese medicine systems, and analysis platform. The related targets of SGR were obtained by Genecards, connective tissue disease, therapeutic target database, Drugbank, and Online Mendelian Inheritance in Man database. Moreover, the target information was corrected through UniProtKB and also, this data integrated to draw the "Ingredients-targets" network of SGR. Protein interaction analysis was performed in data platform, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways as well as enrichment analysis on disease-drug target was carried out through metascape online platform. A total of 15 active components were collected from SGR, which correspond to 159 targets; There were 1758 MG-related targets; there are 81 targets related to both drug components and diseases, including 12 key targets. In GO bioaccumulation analysis, 1933 GO items were gathered, which were mainly related to the metabolism of active oxygen species and the active factors of postsynaptic neurotransmitter receptor. According to KEGG analysis, SGR may play a role in the treatment of MG through phosphatidylinositol-3-kinase-protein kinase B signaling pathway, T-cell receptor, cAMP, tumor necrosis factor (TNF), and interleukin-17 (IL-17) signaling pathway, Th17 cell differentiation, endocrine resistance, hepatitis, and some cancer pathways. This study shows that SGR mainly treat myasthenia gravis through the regulation of TNF, MAPK1, JUN, TP53 and other targets, T-cell receptor, TNF, and IL-17 signaling pathway, Th17 cell differentiation and other pathways, which reflects the characteristics of multicomponent, multitarget, and multichannel of traditional Chinese medicine, and providing a certain pharmacological basis for the follow-up study.

Clinical Genomic, phenotype and epigenetic insights into the pathology, autoimmunity and weight management of patients with Myasthenia Gravis (Review).

Myasthenia Gravis (MG) is an autoimmune disease that affects neuromuscular junctions and is characterized by muscle weakness as a result of autoantibodies against certain proteins. As a heterogeneous disorder, MG presents with different types, including neonatal, ocular and generalized in both juveniles and adults. Different types of antibodies serve a role in how MG presents. The main biological characteristic of MG is the production of antibodies against the muscular acetylcholine receptor; however, other types of antibody have been associated with the disorder. The role of the thymus gland has been established and thymectomy is a possible treatment of the disease, along with traditional medication such as pyridostigmine bromide (Mestinon) and immunosuppresants. In recent years, steps have been made towards developing more sensitive diagnostic methods. Additionally, novel treatments have demonstrated promising results. Developing new assays may lead to an increased understanding of the disease and to unravelling the genetic pathway that leads to the development of neuromuscular diseases.

Morvan's syndrome and myasthenia gravis related to familial Mediterranean fever gene mutations.

BACKGROUND: We present the first case of Morvan's syndrome (MoS) and myasthenia gravis (MG) related to familial Mediterranean fever (FMF) gene mutations. CASE PRESENTATION: A 40-year-old woman with a 1-year history of bilateral ptosis and limb muscle weakness presented to our hospital. She also had memory impairment, insomnia, hyperhidrosis, and muscle twitches. Electromyography confirmed widespread myokymia, and there was evidence of temporal region dysfunction on electroencephalography. Anti-voltage-gated potassium channel complex antibodies and anti-acetylcholine receptor antibodies were both positive. Edrophonium administration was effective for bilateral ptosis and muscle weakness. She and her family experienced self-limiting febrile attacks with arthralgia, which led us to suspect FMF. Genetic analyses revealed compound heterozygous mutations in exon 2 of the MEFV gene (L110P/E148Q). From these findings, a diagnosis of MoS and MG complicated with MEFV gene mutations was made. Intravenous high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin resulted in only transient, limited improvement, and frequent relapses, especially in the myasthenic symptoms. Interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α were markedly elevated in the serum, which was considered to be derived from the MEFV mutations and responsible for the resistance to immunotherapy. CONCLUSION: The present case illustrates a possible link between auto-inflammation and auto-antibody-mediated neurological diseases.

DNA microarray in search of new drug targets for myasthenia gravis.

DNA microarray technology was used to identify new potential drug targets for myasthenia gravis (MG), to delineate genes involved in the pathogenesis of the disease and to possibly target their protein products for immunotherapy. In this study we compared the gene expression in lymph node cells (LNC) and muscles of rats with experimental autoimmune MG (EAMG) to those of control, healthy rats. Of the genes that were found to be deregulated in EAMG, we chose to elaborate on two gene systems: (a) The chemokine IFN-gamma-inducible protein 10 (IP-10, CXCL10), and its receptor (CXCR3) and (b) phosphodiesterases.

[Reduction of genotoxic damage in oral mucosa with myasthenia gravis by traditional Chinese medicine].

Micronucleated exfoliated cell (MEC) of oral mucosa of 40 patients with myasthenia gravis (MG) and 54 normal controls were observed by means of micronucleus test. The frequency of MEC of two groups were 9.56/1000 and 2.55/1000 respectively, and their difference was remarkably significant (P < 0.001). 22 cases were treated by TCM Qiang Ji Jian Li Capsule. The frequency of MEC after treatment fell from 14.38/1000 to 6.00/1000. The difference was significant (P < 0.002). The frequency of Spleen-asthenia group higher than that of non-Spleen-asthenia (P < 0.05). The results revealed that. The patients with MG had genotoxic damage. (2) The constitution with the Spleen-asthenia and the genotoxic damage was related. (3) Qiang Ji Jian Li Capsule of invigorating the Spleen and benefiting Qi could reduce the genotoxic damage.