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Disease-modifying therapies used to treat multiple sclerosis and the gut microbiome: a systematic review

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Abstract

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.

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Data availability

All reported data are based on already published work; no novel data were reported.

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Acknowledgements

We would like to thank Vanessa Kitchin (librarian, University of British Columbia Faculty of Medicine) for assistance in refining the search strategy used in this review. This study was supported, in part, by the 2022 UBC Multiple Sclerosis Connect Program Summer Studentship Award funded by the Christopher Foundation (recipient: CT).

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Authors and Affiliations

  1. Division of Neurology, Faculty of Medicine, Djavad Mowafaghian Centre for Brain Health, Room S126, 2211 Wesbrook Mall, University of British Columbia, Vancouver, BC, V6T 2B5, Canada

    Chia-Chen Tsai, Sophia Jette & Helen Tremlett

  2. Faculty of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada

    Chia-Chen Tsai

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  1. Chia-Chen Tsai
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Corresponding author

Correspondence to Helen Tremlett.

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Conflicts of interest

CT received support from the 2022 University of British Columbia (UBC) MS Connect Summer Studentship Award funded from the Christopher Foundation to conduct this work. CT receives funding from the Consortium of MS Centres and has had travel expenses reimbursed by MS Canada. SJ reports no disclosures. HT has, in the last 5 years, received research support from the Canada Research Chair Program, the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada, the Multiple Sclerosis Scientific Research Foundation and the EDMUS Foundation (‘Fondation EDMUS contre la sclérose en plaques’); in addition, in the last 5 years, has had travel expenses or registration fees prepaid or reimbursed to present at CME conferences from the Consortium of MS Centres (2018, 2023), National MS Society (2016, 2018, 2022), ECTRIMS/ACTRIMS (2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023), and American Academy of Neurology (2015, 2016, 2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by HT’s research group.

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Tsai, CC., Jette, S. & Tremlett, H. Disease-modifying therapies used to treat multiple sclerosis and the gut microbiome: a systematic review. J Neurol 271, 1108–1123 (2024). https://doi.org/10.1007/s00415-023-12107-0

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