The Role of Gut Microbiota in Neuromyelitis Optica Spectrum Disorder

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, disabling inflammatory disease of the central nervous system (CNS). Aquaporin-4 (AQP4)-specific T cells play a key role in the pathogenesis of NMOSD. In addition to immune factors, T cells recognizing the AQP4 epitope showed cross-reactivity with homologous peptide sequences in C. perfringens proteins, suggesting that the gut microbiota plays an integral role in the pathogenicity of NMOSD. In this review, we summarize research on the involvement of the gut microbiota in the pathophysiology of NMOSD and its possible pathogenic mechanisms. Among them, Clostridium perfringens and Streptococcus have been confirmed to play a role by multiple studies. Based on this evidence, metabolites produced by gut microbes, such as short-chain fatty acids (SCFAs), tryptophan (Trp), and bile acid (BA) metabolites, have also been found to affect immune cell metabolism. Therefore, the role of the gut microbiota in the pathophysiology of NMOSD is very important. Alterations in the composition of the gut microbiota can lead to pathological changes and alter the formation of microbiota-derived components and metabolites. It can serve as a biomarker for disease onset and progression and as a potential disease-modifying therapy.

Keywords: gut microbiota; metabolites; neuromyelitis optica spectrum disorders.

Figure 1

Pathogenesis of NMOSD and the role of gut microbiota. It is thought that an impaired immune system may promote naive T cell transformation into Th 17 cell and stimulate B cell differentiation to plasmablasts, then to plasma cells producing AQP4-IgG autoantibody. Interleukin 6 (IL-6) is a key factor in AQP4-related NMOSD pathophysiology. Besides IL-6, Th17 cells differentiation may be induced by IL-17 and IL-21(shown in small black arrows). A leaky BBB contributes to the migration of AQP4-IgG from the periphery into the CNS. AQP4-IgG bind to AQP4 and activate the complement cascade. Activated complement leads to leukocyte infiltration, particularly neutrophil and eosinophil, and results in astrocyte damage and demyelination. The gut microbiota has also been found to be involved in the pathogenesis of NMOSD. Metabolites produced by gut microbiota (shown in deep blue arrows) can pass through the damaged BBB and regulate T cells and B cells through multiple pathways (shown in long black arrows). Communication between the immune gut microbiota and the CNS may be driven by the microbiota–gut–brain axis.