Elsevier

Clinical Immunology

Volume 235, February 2022, 108379
Clinical Immunology

Review Article
Role of diet in regulating the gut microbiota and multiple sclerosis

https://doi.org/10.1016/j.clim.2020.108379Get rights and content

Introduction

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) that affects 2.5 million people worldwide [1]. There is currently no cure for MS; however, recent studies demonstrating the influence of diet and the gut microbiota on disease suggest new therapeutic avenues. While nutrition and microorganisms have previously been associated with MS through epidemiological studies, several factors have contributed to the resurgence in attention towards the host-microbe axis. First is the recognition of the importance of the gut microbiota in the development of host immunity. Second is the establishment of gnotobiotic mouse models that allow for more precise investigation of the gut microbiota. Third is a greater appreciation for the role of metabolism, and, by extension, host dietary intake, in host immune function. While difficult to study, the multi-directional relationship between host diet, commensal gut microbiota, and host immunity will be important to understand in order to leverage diet and microbiota-based interventions for the benefit of MS patients.

In this review, we discuss major dietary components and diet regimens that have been associated with MS and the most commonly used preclinical model of MS, experimental autoimmune encephalomyelitis (EAE). We examine recent evidence supporting the role of commensal gut microbiota in the development and progression of disease. We further consider our current understanding of the relationship between host diet and commensal gut microbiota generally before highlighting studies addressing this relationship in the context of EAE and MS. Lastly, we close by posing critical questions related to the interactions between diet, gut microbiota, and MS that must be answered in order to translate diet- and microbiota-based therapies to MS patients.

Section snippets

Diet and multiple sclerosis

It is important to precede a review of the literature concerning diet and MS with a note that multiple systematic reviews of dietary intervention trials for MS find no strong evidence for the use of diet in treating MS due to the lack of robust clinical trial design [2,3]. These systematic reviews do not necessarily dismiss the potential benefit of nutritional intervention in MS, but they highlight the challenges of studying dietary interventions in disease. First, many dietary studies use

Gut microbiota and multiple sclerosis

Closely tied to diet is the role of the commensal gut microbiota in MS. This is unique from the role of infection in MS, which has been associated with an increased risk of developing MS and exacerbation of MS symptoms [[168], [169], [170], [171], [172]]. In contrast to these more transient host-pathogen interactions, host-commensal interactions have effects on physiology throughout the host's lifespan. In the context of demyelinating disease, this is most evident in germ-free mice that lack an

Discussion

Whether using the top-down, bottom-up, or unbiased approach to dissect diet, microbiota, and disease relationships, it is clear that such networks are complex. The difficulty in understanding the interplay between these factors is magnified by tentative results of diet and probiotic treatments in MS patients that require validation in larger, longer clinical trials. Outstanding questions in this area are: Does the benefit of vitamin D supplementation, the most studied dietary intervention in

Acknowledgements

This work was supported by the National Institutes of Health 5R01NS065714, 1R01NS091939 and 5T32AI055434 (J.M.S.S.).

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