Abstract: Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. The gut microbiota (GM) and its metabolites crucially regulate immune responses and inflammation in MS pathogenesis via the “gut-brain” axis. However, existing studies predominantly focus on compositional phenotypes and conventional immune pathways, highlighting an urgent need to systematically dissect the micro-level molecular networks mediated by core metabolites. This review summarizes recent advances in key metabolites—short-chain fatty acids, indole derivatives, and bile acids—and explores their networked regulatory roles bridging peripheral immunity and central neuropathology. By multidimensionally elucidating these mechanisms, we aim to provide a theoretical basis for developing novel clinical biomarkers and microbiota-targeted interventions.

Key words: multiple sclerosis, gut microbiota, gut microbiota metabolites, short chain fatty acid, indole derivatives, bile acid