Microbiome-Derived Metabolites in Multiple Sclerosis: Mechanisms of Immune Regulation and Therapeutic Potential: A Literature Review

Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease characterized by immune dysregulation, demyelination, and neurodegeneration of the central nervous system (CNS).Increasing evidence suggests that gut microbiota and microbiome-derived metabolites play important roles in the pathogenesis and progression of MS by modulating the gut-brain-immune axis.This narrative review examines the possible immunomodulatory effects of microbiome-derived metabolites in MS, with particular emphasis on short-chain fatty acids (SCFAs), tryptophan-derived metabolites, and polyamines, and evaluates their potential therapeutic implications.This review was conducted using the most recent available studies relevant to the topic.The search included PubMed, Google Scholar, and PMC databases.Eligible studies focused on randomized controlled trials, systematic reviews, meta-analyses, observational studies, reviews, and other publications that examined the role of microbiota and its metabolites in MS.The reviewed evidence indicates that MS-associated dysbiosis is accompanied by altered microbial metabolite production, disruption of regulatory T cell (Treg)/T helper 17 (Th17) balance, impaired barrier integrity, and increased neuroinflammation.SCFAs, tryptophan-derived metabolites, and polyamines demonstrate immunoregulatory effects through modulation of T-cell responses, cytokine signaling, and inflammatory pathways.Microbiota-targeted interventions, including probiotics, prebiotics, dietary modulation, and metabolite supplementation, have shown promising immunological and clinical effects.However, methodological heterogeneity, small cohorts, variable interventions, and insufficient long-term clinical validation limit definitive conclusions regarding therapeutic efficacy.Future large-scale longitudinal and multi-omics studies are crucial for clarifying the underlying mechanisms and unlocking microbiotatargeted strategies to manage MS more effectively.