Exploring the Role of Neuroinflammation and Gut-Brain Axis Dysregulation in the Pathogenesis of Non-Motor Symptoms in Myasthenia Gravis

ანოტაცია

Myasthenia gravis (MG) is a long-lasting autoimmune neuromuscular disorder usually reflected by the presence of autoantibodies against acetylcholine receptors at the neuromuscular junction and characterized by either ocular or generalized disease with possible respiratory crisis. The situation has not changed, as diagnostic difficulties and recurrences are still the main problems despite the improvements in diagnostics and immunosuppression. Moreover, the totality of the evidence is pointing to the fact that MG is a disease that also has non-motor manifestations of important clinical significance. The aim of this narrative review was to summarize the literature on MG which takes the position of a multisystem neuroimmune disease and to clarify the mechanisms of immune dysregulation, neuroinflammation, and gut-immune-brain axis that are the cause of the non-motor symptoms such as fatigue, cognitive impairment, mood disturbances, sleep changes, and autonomic dysfunction. A thorough search in PubMed and Google Scholar using terms connected to MG, non-motor symptoms, gut microbiota, gut-brain axis, neuroinflammation, and immune dysregulation led to the discovery of full-text English studies highlighting both systemic and central mechanisms; a qualitative synthesis of themes was drawn up and focused on microbiome composition, metabolites, cytokines, and the changes in immune cells. Studies were consistent in correlating MG with diminished variety of gut microbes, loss of Firmicutes (including Clostridia/Lachnospiraceae and Faecalibacterium) producing butyrate, and increase in munificent taxa (e.g., Streptococcus and Enterococcus), which was in line with Treg cell (Treg) function being diminished and Th17/Treg balance being shifted. The research involving multi-omics techniques pointed toward the conclusion that dysbiosis was a major reason for the widespread disturbance of SCFAs, and also that it disrupted the pathways of KP and BA through the action of receptors such as AhR and TGR5, which was reflected in the metabolomic profile changes of feces (e.g., of cytosine, xanthine, adenine, and methylmalonic).