Disease-modifying therapy for multiple sclerosis: Implications for gut microbiota

Background: Growing evidence has suggested the involvement of gut microbiota in the pathophysiology of multiple sclerosis (MS). Disease-modifying therapies (DMTs) exert a parallel effect on the gut microenvironment with subsequent modulation of the intestinal and systemic immune system. Herein, we summarize the current literature on the effect of DMTs on the gut microbiome and possible implications for MS. Methods: All the literature available in PubMed on the effects of DMTs on the gut microbiota composition in patients with MS was reviewed. We used multiple combinations of the following keywords: "multiple sclerosis; demyelinating disease; gut microbiome; microbiome; brain-gut axis; diet; fecal microbiome; disease modifying therapy; immunomodulator; interferon; glatiramer acetate; teriflunomide; dimethyl fumarate; natalizumab; alemtuzumab; anti-CD20; fingolimod". All the original research articles available in English were included in this narrative review. Results: Ten original full-text articles were considered eligible, including seven case-control and three cohort studies. First-line DMTs, including oral and subcutaneous treatments (dimethyl fumarate, glatiramer acetate, and interferon β 1b) were considered, while a small number of patients with MS were under natalizumab, fingolimod and anti-CD20 treatments. Conclusions: Emerging evidence reported changes in the gut microbiome during exposition to DMTs. However, the association between DMTs exposure and microbial changes was mostly indirect, and the results of the different studies needed to be more consistent. The mitigation of methodological bias is necessary for future studies to allow the identification of a "microbial signature" related to MS pathophysiology, the role of DMTs, and possible prognostic implications.