Dottorato in PLASTICITÀ NEUROSENSORIALE

Titolo della tesi: Multiple Sclerosis Gut Microbiome Instability, Link to Disability, and Lesion Load

Background and Objective: Multiple sclerosis (MS) progression is influenced by both genetic and environmental factors. Several studies of autoimmune diseases suggest that gut microbiome changes modulate the immune response. We characterized the gut microbiome composition in patients with MS (active and stable) relative to healthy controls (HC), and with respect to disease duration, disability, and radiographic progression of the disease. Methods: We collected and analyzed stool microbiome and MRI data across patients representing MS; a portion of the study population was followed longitudinally. Paired household members served as HC. Results: A total of 44 patients were included in the analysis—33 MS (27 with relapsing remitting (RR) MS, 3 with primary progressive (PP) MS, 3 with secondary progressive (SP) MS; 23 with active disease, 10 with stable disease status) and 11 healthy controls (HC). The MS and HC groups differed significantly by age, gender, and BMI but not by race. Patients were considered to have an active status if they presented with new clinical symptoms, exam findings and/or new lesion/enhancement on MRI. Of the 5 MS subjects followed longitudinally, 3 subjects switched from active to stable disease status. Six HC were followed longitudinally. Faecalibacterium prausnitzii and Roseburia hominis were more abundant in the control group than in the MS population. The gut microbiome composition in patients with MS was less stable than HC. Clostridium leptum abundance increased with more severe neurological disability. When analyzing timed 25-foot-walk data, Alistipes shahii is linked to worse walk speed while Parabacteroidesis associated with better scores. Ruminococcus bromii and Subdoligranulum are more abundant in patients with a more recent disease onset. Veillonella is the most abundant species in those with the highest number of new T2 brain lesions among those with MS. Discussion: We find that patients with MS have a more unstable gut microbiome composition than healthy controls and that there are specific gut microbiome associations both with MS disease duration, disability, and radiographic progression of the disease.