STUDY OF THE INTESTINAL MICROBIOTA IN RELAPSING REMITTING MULTIPLE SCLEROSIS TOWARDS NEW POTENTIAL TREATMENTS

Multiple sclerosis (MS) is a chronic demyelinating inflammatory disease of the central nervous system (CNS). The most frequent form is represented by the relapsing-remitting one (RRMS). Studies revealed that many genes associated with the differentiation, activation, and proliferation of CD4+ helper T cells are linked to MS susceptibility. In particular, the most involved are CD4+ T helper 1 (Th1) and T helper 17 (Th17) lymphocytes. Although the etiology and pathogenesis of MS remains unclear, it is known that the cause of MS is multifactorial and includes genetic predisposition together with environmental factors. Among the latter ones, bacterial or viral infections are listed. In the last years, evidence showed that MS patients have an altered gut microbiota (intestinal dysbiosis) and that specific bacteria could be used to relieve disease symptoms in a mouse model. Since several studies have shown that probiotics (live microorganisms promoted with claims that they provide health benefits) and prebiotics (high-fiber foods that act as food for human microflora) can modulate microbial community and improve gastrointestinal symptoms and multi-organ inflammation in different pathologies including MS, the aims of this thesis were to study the gut microbiota in Sicilian MS patients to identify the bacteria inducing intestinal dysbiosis. Moreover, given the correlation between the onset of multiple sclerosis and infectious diseases, the spread of two pathogens (Bartonella henselae and Mycoplasma mycoides) related to MS in the environment and their presence in the MS patients were evaluated. Eventually, the biological activities of root extracts of the Helleborus bocconei plants, endemic in Sicily, were studied to understand whether these molecules may possess anti-inflammatory activity in MS. The main results of this research project are shortly listed below. The microbiota study revealed a higher abundance in MS patients of bacterial species correlated with the inflammatory state: Ruminococcus lactaris, Alistipes putredinis, Gemmiger formicilis and Bacteroides caccae. Although B. henselae and M. agalactiae were isolated in the analyzed environments, they were not found in MS patients. H. bocconei extracts induced a reduction in IL-1β and iNOS gene expression of peripheral blood mononuclear cells (PBMCs) suggesting their potential use as mediators of the inflammatory response. Finally, H. bocconei butanol extracts showed potential anti-viral activity against the Herpes virus, one of the main risk factors of MS. Thus, Helleborus extracts could be exploited as a therapy to reduce the inflammatory state of MS patients.