Disease-modifying Therapies Used to Treat Multiple Sclerosis and the Gut Microbiome: a Systematic Review

Background: The gut microbiome may play a role in multiple sclerosis (MS). However, its relationship with the disease-modifying therapies (DMTs) remains unclear. We systematically reviewed the literature to examine the relationship between DMTs and the gut microbiota among persons with MS (pwMS).

Methods: MEDLINE, EMBASE, Web of Science, and Scopus were searched (01/2007-09/2022) for studies evaluating potential gut microbiota differences in diversity, taxonomic relative abundances, and functional capacity between DMT-exposed/unexposed pwMS or before/after DMT initiation. All US FDA-approved MS DMTs (1993-09/2022) and rituximab were included.

Results: Of the 410 studies, 11 were included, totalling 1243 pwMS. Of these, 821 were DMT exposed and 473 unexposed, including 51 assessed before/after DMT initiation. DMT use duration ranged from 14 days to > 6 months. No study found a difference in gut microbiota alpha-diversity between DMT exposed/unexposed (p > 0.05). One study observed a difference in beta-diversity between interferon-beta users/DMT non-users (weighted UniFrac, p = 0.006). All studies examined taxa-level differences, but most (6) combined different DMTs. Two or more studies reported eight genera (Actinomyces, Bacteroides, Clostridium sensu stricto 1, Haemophilus, Megasphaera, Pseudomonas, Ruminiclostridium 5, Turicibacter) and one species (Ruthenibacterium lactatiformans) differing in the same direction between DMT exposed/unexposed. DMT users had lower relative abundances of carbohydrate degradation and reductive tricarboxylic acid cycle I pathway than non-users (p < 0.05), but findings could not be attributed to a specific DMT.

Discussion: While DMT use (versus no use) was not associated with gut microbiota diversity differences, taxa-level differences were observed. Further work is warranted, as most studies were cross-sectional, few examined functionality, and DMTs were combined.