Targeting the gut to treat multiple sclerosis

Document Type

Article

Abstract

The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies and cohorts vary greatly. Small clinical and preclinical trials in pwMS and mouse models, in which microbial composition was manipulated through the use of antibiotics, fecal microbiota transplantation, and probiotic supplements, have provided promising outcomes in preventing CNS inflammation. However, results are not always consistent, and large-scale randomized controlled trials are lacking. Herein, we give an overview of how the GBA could contribute to MS pathogenesis, examine the different approaches tested to modulate the GBA, and discuss how they may impact neuroinflammation and demyelination in the CNS.

Medical Subject Headings

Animals; Autoimmunity; Disease Models, Animal; Dysbiosis (immunology, physiopathology); Endocrine System (immunology, physiopathology); Enteric Nervous System (immunology, microbiology, physiopathology); Fecal Microbiota Transplantation; Gastrointestinal Microbiome (drug effects, immunology, physiology); Humans; Intestinal Mucosa (immunology, microbiology, physiopathology); Models, Neurological; Multiple Sclerosis (etiology, microbiology, therapy); Neuroimmunomodulation; Probiotics (therapeutic use)

Publication Date

7-1-2021

Publication Title

The Journal of clinical investigation

E-ISSN

1558-8238

Volume

131

Issue

13

PubMed ID

34196310

Digital Object Identifier (DOI)

10.1172/JCI143774

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