Intestinal Microbiota and Multiple Sclerosis: towards new therapeutic approaches

Multiple sclerosis (MS) is a disease of the central nervous system characterized by chronic inflammation and immune-driven demyelination. To date, the etiopathogenesis of the disease remains unclear, although it is believed that a combination of genetic and environmental factors contributes to its onset. Among the environmental factors, growing evidence highlights the role of the gut microbiota in both the onset and progression of the disease. Indeed, the gut microbiota constitutes a complex community of microorganisms capable of interacting with both the immune system and the central nervous system through the gut–brain axis. Furthermore, several factors can influence the composition and function of the gut microbiota, potentially affecting disease progression. Among these, diet and pharmacological therapies are particularly discussed. The first aim of this study was to evaluate the dietary habits in people with MS (pwMS) and to test whether adherence to the Mediterranean Diet (MD) could have an impact on the severity of the disease measured as the MS severity score (MSSS). Adherence to the MD was assessed in 31 PwMS using the Mediterranean Diet Adherence Screener (MEDAS), the Pyramid-based Mediterranean Diet Score (PyrMDS) index, and the Italian Mediterranean Index (IMI), and their eating habits were recorded in a food diary for a one-year follow-up. When data obtained from dietary analysis were compared to the MSSS, results showed that pwMS with lower MSSS adhere more to the MD than the other pwMS groups according to the MEDAS index. Furthermore, a high consumption of fiber in the MS mild severity class was observed. Then, the gut microbiota impact on disease severity and worsening was investigated. This study analyzed the gut microbiome of 58 treatment-naïve pwMS and 18 Healthy Donors (HD) using shotgun metagenomic sequencing combined with clinical features collected over one year from the diagnosis. We found that glucocorticoid treatment at disease onset significantly impacted bacterial and eukaryotic diversity. PwMS were then stratified according to their lesion burden, lesion localization, and magnetic resonance imaging (MRI) activity, revealing distinct microbial signatures associated with clinical features. Using a novel approach, we identified a core microbial signature comprising five species—Phocaeicola vulgatus, Bacteroides ovatus, Bacteroides xylanisolvens, Alistipes onderdonkii, and Roseburia intestinalis—that can stratify MS patients based on prognostic factors. Finally, we aimed to investigate the impact of Dimethyl fumarate (DMF) therapy, commonly used for the treatment of MS, on gut microbiota composition. To this end, the gut microbiota of 25 patients, both treatment-naive and non-naïve, was analysed using shotgun metagenomic sequencing over a one-year follow-up period. The analysis included bacterial, archaeal and eukaryotic populations. A statistically significant difference in bacterial observed alpha diversity was observed between baseline and T1, which persisted between 8 baseline and T12. Moreover, a statistically significant difference in beta diversity among groups at different timepoints was also observed for Eukarya. Lastly, differentially abundant species for each timepoint were obtained. Collectively, these findings highlight the critical role of the diet and gut microbiota in the context of MS, both at disease onset and throughout its progression. This underscores its potential as both a therapeutic target and a prognostic early biomarker for MS