Toward regionally equitable precision medicine: microbiota‑associated mechanisms and emerging personalized strategies in multiple sclerosis.

Abstract

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system in which dysregulated immune signalling and barrier dysfunction play central pathogenic roles. Increasing evidence implicates the gut microbiota as a key modulator of host immune homeostasis; however, current understanding is largely derived from Western cohorts and remains fragmented at the mechanistic level. This review synthesizes global evidence alongside emerging data from underrepresented regions, including Egypt, Iran, and India, to delineate molecular pathways linking MS-associated dysbiosis to immune dysregulation. Across studies, dysbiosis is consistently associated with impaired short-chain fatty acid-mediated immunoregulation, skewing toward proinflammatory Th1/Th17 responses, and disruption of intestinal and blood-brain barrier integrity, with region-dependent functional signatures involving oxidative stress and neurotransmitter and tryptophan metabolism. Several regional signatures reported here derive from a single pilot-scale cohort and should be regarded as hypothesis-generating pending independent validation, and current microbiota-targeted interventions remain investigational rather than established disease-modifying therapies for MS. We critically examine microbiota-derived signals, including short-chain fatty acids, lipopolysaccharide, and polysaccharide A, that modulate dendritic cell programming, regulatory T-cell differentiation, and neuroinflammatory cascades. We further evaluate microbiome-targeted therapeutic strategies and discuss how sex, regional context, and sequencing methodology influence functional interpretation and therapeutic responsiveness. Finally, we propose a roadmap for regionally equitable precision medicine, advocating for standardized multi-omics and culturally inclusive longitudinal designs to move beyond empiric interventions toward personalized, strain-defined biotherapeutics tailored to the unique microbial and environmental landscapes of MS patients worldwide.