NMOSD is a rare autoimmune disease targeting the central nervous system strongly associated with anti-AQP4 antibodies. There is a significant need for robust epidemiological surveillance of NMOSD, with projected prevalence of 0.52-10 per 100,000 globally with female predominance. NMOSD has also been associated with C. perfringens related gut dysbiosis, with C. perfringens expressing epitopes similar to AQP4. Given the need for research into the relationship between the gut-brain-immune axis and NMOSD, we conducted a literature review to assess the role of the microbiome in NMOSD incidence and progression.

A literature review of PubMed yielded 30 publications published between May 2008 and July 2024. Keywords Used: (Clostridium perfringens AND neuromyelitis optica) OR (gut dysbiosis AND NMOSD) OR (molecular mimicry AND aquaporin-4) OR (gut microbiota AND NMO) OR (ABC transporter Clostridium AND autoimmune response). 

Microbial antigens resembling host proteins can trigger CD4+/CD8+ T-cell mediated autoimmune response, potentially leading to CNS damage. Due to homology between C. perfringens and AQP4 peptides (e.g., p66- p75), proliferation in NMO patient can promote Th17 polarization and inflammation, as well as strong T-cell responses in NMOSD. Potential synergistic responses in NMO exacerbation may be seen in hyperproliferation of other enteric pathogens (e.g., C. boltege, H. pylori).

Abundance of C. perfringens in the gut microbiome may be contributing to the pathology of NMOSD. The gut dysbiosis was accompanied by changes in epithelial barrier and immune cell composition, signaling compromised barrier integrity and gut inflammation or immune dysregulation. In addition to C. perfringens, other organisms may contribute to the pathogenesis of NMOSD like C. bolteae, which shares sequence homology with AQP4. These findings highlight the need for further investigation into the role of these organisms in NMOSD pathology.