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Review
. 2022;20(7):1413-1426.
doi: 10.2174/1570159X19666210629145351.

Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications

Xu Wang  1 , Zhen Liang  1 , Shengnan Wang  1 , Di Ma  1 , Mingqin Zhu  1 , Jiachun Feng  1
Affiliations
Review

Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications

Xu Wang et al. Curr Neuropharmacol. 2022.

Abstract

The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota have also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.

Keywords: Gut microbiota; antibiotic treatment; blood-brain barrier; fecal microbiota transplantation; gut-microbiota-brain axis; multiple sclerosis; neuro-inflammatory diseases; probiotic microbiota.

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Figures

Fig. (1)
Fig. (1)
The mechanism of the gut microbiota involment in the initiation and development of MS. Gut microbiota might active the auto-reactive T cells in GALT via mimicry or/and other pathway through disrupted intestinal barrier. Besides, they might also induce the production of auto-antibodies through the stimulation of APC and the activation of B cells. The decrease of anti-inflammatory metabolites (such as SCFAs) and the enhancement of pro-inflammatory signals (such as salic acids metabolism) caused by the dysbiosis of gut microbiota could suppress the differentiation of Treg cells and promote the expansion of Th1 and Th17 cells. In addition, several toxic microbiota components and metabolites (including LPS and LTA) might enter into blood and contribute to the destruction of BBB. Subsequently, Th1, Th17 and auto-reactive T cells can infiltrate the CNS through disrupted BBB, resulting in the inflammation in CNS and the injury of myelin and neurons damage. In turn, the inflammation CNS may also recruit more inflammatory immune cells and cytokines, aggravating the CNS injury. APC, antigen presenting cell; BBB, blood brain barrier; CNS, central nervous system; GALT, gut associated lymphoid tissue; LPS, lipopolysaccharide (LPS); LTA, lipoteichoic acid; SCFAs, short-chain fatty acids.
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