Microbial-Immune Interplay in CNS Autoimmune Diseases: Lessons from Animal Models and Clinical Studies

The gut microbiota plays a key role in shaping and educating host immunity, and it may also influence the central nervous system (CNS). Changes in the composition and function of commensal microbes can trigger inflammation and abnormal immune activation, contributing to disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AIE), neuropsychiatric lupus (NPSLE), and narcolepsy. The microbiota has been linked to disease risk or protection via the production of its metabolites, products, or antigens that could modulate host immune responses, consequently causing CNS inflammation. This review highlights patient studies investigating the mechanisms through which the human microbiota is involved in CNS autoimmunity by modulating the host immune system. Future research should focus on defining causal relationships, elucidating molecular mechanisms, and addressing the different members of the intestinal microbiota to translate microbiota modulation into clinical interventions for CNS autoimmune diseases.