Difficult relationships between humans and bacteria: associations between multiple sclerosis and the human microbiome

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, the pathogenesis of which involves complex interactions between genetic predisposition, environmental factors, and dysregulation of immune responses. This review critically synthesizes available evidence from studies demonstrating significant alterations in the composition of the human microbiome in individuals with MS. The work summarizes the current state of knowledge regarding the composition, diversity, and dysbiosis of the gut microbiome in MS, highlighting the heterogeneity of observed microbial changes depending on clinical disease phenotype, inflammatory activity, therapeutic interventions, and methodological across studies. Data from other microbial niches are also considered, including the oral and skin microbiome, as well as mucosal-associated intestinal microbiota, which may contribute to local and peripheral modulation of immune responses. The gut mycobiome is presented as a complementary component whose potential immunological relevance is currently under investigation. Observational and experimental evidence suggest that alterations in microbiota composition correlate with immune gene expression and with the differentiation of effector T cell populations, particularly along the Th17/IL-17 axis, although the casual significance of these associations in human MS remains unclear. Host genetic factors, particularly HLA class II gene polymorphisms, may also influence microbiota composition and susceptibility to autoimmunity. Furthermore, microbiome-derived metabolites detected in plasma and cerebrospinal fluid may mediate communication between the gut and the central nervous system. Overall, the available evidence points to multilevel interactions between the microbiome, host genetics, metabolism, and the immune system in MS. However, substantial methodological heterogeneity, predominantly cross-sectional study designs, treatment-related confounding, and limited reproducibility of taxon-specific findings currently restrict causal interpretation. Further longitudinal studies in patients with MS are therefore needed to determine whether microbiome alterations contribute to MS development and progression or occur as consequence of the disease and its treatment.