The gut microbiota-miRNA axis in multiple sclerosis: Mechanisms and therapeutic potentials

Multiple sclerosis (MS) is a chronic immune-mediated neuroinflammatory and neurodegenerative disease characterized by demyelination, blood-brain barrier disruption, and progressive neurological disability. Increasing evidence identifies the gut microbiota (GM) as a key environmental factor in MS pathogenesis, with microbial dysbiosis contributing to immune dysregulation, impaired intestinal barrier integrity, and chronic systemic inflammation. At the same time, microRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators of immune responses, neuroinflammation, and neurodegeneration. Recent studies further indicate that the GM and host miRNAs engage in a dynamic bidirectional interaction, whereby microbial metabolites modulate host miRNA expression, while host-derived miRNAs influence microbial composition and function. This reciprocal crosstalk has emerged as an important mechanism linking intestinal homeostasis to central nervous system immunity and disease progression in MS. In this review, we comprehensively summarize current evidence on the GM-miRNA axis and its role in MS pathophysiology, highlighting the molecular mechanisms underlying host-microbiota communication and immune regulation. We also discuss emerging microbiota- and miRNA-targeted therapeutic strategies, including fecal microbiota transplantation, probiotics, and miRNA-based therapeutics, as potential approaches for restoring immune homeostasis and attenuating neuroinflammation. Finally, we address current challenges, knowledge gaps, and future research directions required to translate these findings into clinical practice. A better understanding of the GM-miRNA axis may facilitate the development of novel biomarkers and personalized therapeutic strategies, ultimately shifting MS management from symptomatic treatment toward precision, disease-modifying interventions.