The Gut Microbiome in Adult Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Observational

Summary: 
      This study aims to assess the following research questions:

        1. Map and benchmark the gut microbiome of patients with RRMS, and PPMS versus matched
           healthy controls

        2. Determine whether RRMS or PPMS have a unique bias for a gut microbiome classification
           recently characterized.

        3. Search for relationship with inflammation, amino acid plasma levels, heart rate
           variability (vagus nerve tone) and hair cortisol as a biological marker of chronic
           stress

        4. Determine whether the gut microbiome is different in MS patients during a relapse.

        5. Determine whether the gut microbiome remains stable after 3 months
    

Detailed description: 
      This study is a prospective multi-center cohort study (University Hospital Brussels, National
      Multiple Sclerosis Center Melsbroek). This is an exploratory study and there is no specific
      outcome on which a power calculation can be made. We will include different subgroups of
      patients with MS: stable non-benign RRMS, PPMS, benign MS [Benign MS is defined as RRMS with
      an EDSS ≤ 3, 15 years after disease onset], RRMS during a relapse (before the administration
      of corticosteroids) [Relapses are defined as the development of new or recurrent neurologic
      symptoms not associated with fever or infection or change in medication, lasting at least 24
      hours, and accompanied by new, objective neurologic findings]. Age and sex matched healthy
      controls will be included as well. All participants will provide a faecal, hair, and blood
      sample twice (baseline and after 3 months). Patients will be assessed clinically at baseline,
      3 months after baseline, and approximately 1, 2, 4.5 years after baseline.

      The results of this study have the potential to identify novel simple strategies to
      strengthen or alter the microbiome ecosystem and strengthen the overall treatment process. In
      case of a positive result, this would form the basis for a follow-up study on medical
      modulation of the microbiome with the aim of finding new treatment options for MS.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This is an exploratory study and there is no specific outcome on which a power calculation
        can be made. We included 122 patients with MS and 30 age and sex matched healthy controls
        as well.
      
Biospecimen description: 
      Fecal specimens from patients will be collected with standard kits and frozen for analysis.

      A blood sample of 10 ml will be drawn from a peripheral vein for the analysis of IL-1beta and
      Il-17 (proinflammatory cytokines) and and IL-10 (anti-inflammatory cytokine), and a range of
      amino acids (released by the gut) through HPLC. A serum sample will be deep frozen for
      further analyses.

      Some hair will be cut at the vertex posterior, close to the skull. A number of 5-10 hairs,
      corresponding to 5 mg, will be collected and stored in a cool place.
    
Keywords: gut microbiome