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Review
. 2023 Dec 20;60(1):6.
doi: 10.3390/medicina60010006.

Impact of Disease-Modifying Therapies on Gut-Brain Axis in Multiple Sclerosis

Ilaria Del Negro  1   2 , Sara Pez  1   2 , Salvatore Versace  1   2 , Alessandro Marziali  1   2 , Gian Luigi Gigli  2 , Yan Tereshko  1   2 , Mariarosaria Valente  1   2
Affiliations
Review

Impact of Disease-Modifying Therapies on Gut-Brain Axis in Multiple Sclerosis

Ilaria Del Negro et al. Medicina (Kaunas). .

Abstract

Multiple sclerosis is a chronic, autoimmune-mediated, demyelinating disease whose pathogenesis remains to be defined. In past years, in consideration of a constantly growing number of patients diagnosed with multiple sclerosis, the impacts of different environmental factors in the pathogenesis of the disease have been largely studied. Alterations in gut microbiome composition and intestinal barrier permeability have been suggested to play an essential role in the regulation of autoimmunity. Thus, increased efforts are being conducted to demonstrate the complex interplay between gut homeostasis and disease pathogenesis. Numerous results confirm that disease-modifying therapies (DMTs) used for the treatment of MS, in addition to their immunomodulatory effect, could exert an impact on the intestinal microbiota, contributing to the modulation of the immune response itself. However, to date, the direct influence of these treatments on the microbiota is still unclear. This review intends to underline the impact of DMTs on the complex system of the microbiota-gut-brain axis in patients with multiple sclerosis.

Keywords: disease-modifying therapies; gut–brain axis; multiple sclerosis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Role of intestinal dysbiosis in the pathogenesis of MS. SCFA-producing anti-inflammatory species (particularly Faecalibacterium and Clostridia) are reduced in MS patients, contributing to the downregulation of regulatory T cell expression and promotion of Th1 and Th17 cell activation. Impaired intestinal permeability in MS patients leads to an increase in autoreactive T cells and a reduced integrity of the BBB [10,11,13,17,18,19]. Translocation of bacterial metabolites and ETX directly affects resident CNS cells (especially microglia and astrocytes) with myelin damage and subsequent demyelination [24,25]. Moreover, BBB breakdown allows activated Th cells and autoreactive immune cells to reach the CNS and intensify central inflammation [4,8]. Legend: MS: multiple sclerosis, PSA: polysaccharide A, SCFAs: short-chain fatty acids, LPS: lipopolysaccharide, IL-10: interleukin-10, IL-17: interleukin-17, INF-y: interferon-y, ETX: epsilon toxin, CNS: central nervous system, BBB: blood–brain barrier. Created by BioRender.com.
Figure 2
Figure 2
Impact of mild- to moderate-efficacy DMTs on gut–brain axis [35,36,39,42,43,44,45,46,47,50,51,52,53,56,57,58,60]. Legend: SCFAs: short-chain fatty acids, IL-10: interleukin-10, INF-β: interferon beta, GA: glatiramer acetate, DMF: dimethyl fumarate, TEF: teriflunomide. Created by BioRender.com.
Figure 3
Figure 3
Impact of high-efficacy DMTs on gut–brain axis [52,66,67,68,69,71,72,75,76,83,92,93,94]. Legend: CD20Ab: anti-CD20 antibodies, S1PRM: sphingosine-1-phosphate receptor modulators. Created by BioRender.com.
See this image and copyright information in PMC

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