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

## TL;DR

This review explores how gut microbes influence the immune system and contribute to autoimmune diseases of the central nervous system, like multiple sclerosis.

## Contribution

The paper synthesizes findings from animal models and clinical studies to highlight the role of the microbiota in CNS autoimmunity.

## Key findings

- Gut microbiota changes can trigger inflammation and immune activation linked to CNS autoimmune diseases.
- Microbial metabolites and antigens modulate host immunity, potentially causing CNS inflammation.
- Future research should focus on causal relationships and molecular mechanisms for clinical translation.

## Abstract

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.

Mechanism of action of the intestinal microbiota on CNS autoimmune diseases. Environmental factors shape gut microbiota composition; dysbiosis alters microbial metabolites and antigenic signals. These modulate innate and adaptive immunity, affect barrier integrity, and influence CNS‐resident cells such as microglia and astrocytes, contributing to immune‐mediated CNS pathology. Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD), autoimmune encephalitis, and neuropsychiatric lupus (NPSLE). The image provided is free of copyright restrictions. Generated with BioRender.