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

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.

Inclusion Criteria:

1. Signed written informed consent.
2. RRMS or PPMS, as defined by the McDonald criteria.
3. Ages 18-65 years.
4. EDSS < 7
5. Treatment with IFN-beta

Exclusion Criteria:

1. SPMS without relapses during the past year at screening.
2. Use of high dose systemic steroids within the last 2 months.
3. Gastrointestinal disease, such as inflammatory bowel disease
4. Use of antibiotics within the last 4 weeks.

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.