Pre-Pro-MS

Treatment tested

• Prebiotics and Probiotics supplementation
• peripheral blood withdrawal
• Transcranial Magnetic Stimulation (TMS)

Placebo or sham

• Placebo supplementation

Other measures (17)

Inclusion Criteria: * RRMS diagnosis, as Polman et al 2011. Ann Neurol. PMID: 21387374 * Age \<= 18 and => 65 years * EDSS score \<= 7 * Disease duration \< 10 years * On DMF or Ocrelizumab treatment from at least 3 months * No corticosteroid administration in the previous month * Ability to provide written informed consent. Exclusion Criteria: * Adverse effects to gadolinium * Blood count basal alteration * Pregnant or lactating women * Vegetarians or vegans * Taking antibiotics, any product or supplement containing probiotics, Omega 3 or other antioxidant supplements within 30 days prior to inclusion * History of food allergies or food intolerance * Clinically significant medical condition other than MS, (latent infections, other autoimmune disease) * Diagnosis of past eating disorders (anorexia, bulimia, or binge eating) or relevant psychiatric disorders.

Inflammatory synaptopathy is a prominent pathogenic process in multiple sclerosis (MS) induced by imbalanced immune system homeostasis. Its persistence causes excitotoxic neuronal damage, leading to motor and cognitive deficits. Although many advances have been made in MS treatment, the development of effective strategies for managing disease progression driven by excitotoxic synaptic dysfunctions is of great significance. Gut dysbiosis is commonly associated with both MS and obesity and high-fat diet (HFD) can exacerbate disease by acting on gut microbiota. Since gut microbiota can shape the immune response and brain functions, we propose to target gut dysbiosis by dietary supplementation of prebiotics and probiotics (Pre-Pro) to treat synaptopathy in both human and experimental model of MS, even when exacerbated by HFD. Overall, this project aims at unveiling the anti-inflammatory and neuroprotective pathways activated by Pre-Pro supplementation to modulate the immune-synaptic axis.