Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study

BACKGROUND: Immunological factors are the key to the pathogenesis of multiple sclerosis (MS). Conjointly, environmental factors are known to affect MS disease onset and progression. Several studies have found that the intestinal microbiota in MS patients differs from that of control subjects. One study found a trend toward lower species richness in patients with active disease versus in patients in remission. The microbiota plays an important role in shaping the immune system. Recent studies suggest the presence of an association between the gut microbiota and inflammatory pathways in the central nervous system. However, the function of this brain-immune-intestine axis and its possible value for predicting treatment effect in MS patients is currently unknown. OBJECTIVE: Our goal is to examine if the changes in gut and oral microbiota and simultaneous changes in the immune response are a predictor for the treatment response in subjects with active relapsing-remitting MS (RRMS) who are being treated with oral cladribine. METHODS: This is a prospective, observational, multicenter study. Eligible subjects are patients with RRMS, between the ages of 18 and 55 years, who will start treatment with oral cladribine. Patients who used probiotics 1 month prior to the start of oral cladribine will be excluded. At baseline (ie, before start) and after 3, 12, and 24 months, the Expanded Disability Status Scale (EDSS) score will be assessed and fecal, oral, and blood samples will be collected. Also, subjects will be asked to register their food intake for 7 consecutive days following the visits. After 24 months, a magnetic resonance imaging (MRI) assessment of the brain will be performed. Responders are defined as subjects without relapses, without progression on the EDSS, and without radiological progression on MRI. RESULTS: Inclusion started in January 2019. A total of 30 patients are included at the moment. The aim is to include 80 patients from 10 participating centers during a period of approximately 24 months. Final results are expected in 2024. CONCLUSIONS: The results of the BIA Study will contribute to precision medicine in patients with RRMS and will contribute to a better understanding of the brain-immune-intestine axis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16162