Gut microbiome profiling at multiple sclerosis onset as a potential early prognostic marker of disease course:...

Alterations in gut microbiome composition have been associated with multiple sclerosis (MS), but their impact on disease severity and early progression remains poorly understood. In this study we investigated whether gut microbiome profiling at diagnosis could identify microbial signatures associated with clinical and radiological features of early MS and provide prognostic information.

We analysed the gut microbiome of 53 treatment-naïve patients with MS (pwMS) and 55 healthy donors (HD) using shotgun metagenomic sequencing, combined with clinical features collected over 1 year from diagnosis. To clarify whether gut microbiome composition at MS onset could have prognostic relevance, pwMS were stratified according to lesion burden, lesion localisation, and magnetic resonance imaging (MRI) activity.

Overall beta diversity in Bacteria, Archaea, and Eukarya differed significantly between pwMS and HD (p-value <0.001, <0.02, <0.03, respectively). Within the MS group, glucocorticoid treatment at disease onset was the clinical factor most strongly associated with gut microbiota diversity. Stratification according to lesion burden, lesion localisation, and MRI activity identified two clinically distinct MS subgroups with different baseline clinical characteristics at onset (p-value <0.03) and different risk of early disease progression. The cluster associated with an unfavourable prognosis showed greater progression within 12 months and was enriched for motor symptoms and spinal cord lesions at diagnosis.

Our findings suggest that gut microbiome alterations are detectable at the earliest stages of MS and are associated with clinical and radiological features linked to short-term disease evolution. Gut microbial profiling may therefore represent a promising early prognostic biomarker and may help to identify candidate targets for early intervention and therapeutic development in MS, although further validation in larger longitudinal cohorts is needed.

This study was supported by grants from the Italian Multiple Sclerosis Foundation, the Cassa di Risparmio di Torino Foundation, and the Italian Ministry of University and Research.