The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis - PubMed (original) (raw)

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The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis

Samantha N Freedman et al. Neurotherapeutics. 2018 Jan.

Abstract

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.

Keywords: Multiple sclerosis (MS); experimental autoimmune encephalomyelitis (EAE); gut microbiome; host–microbe interaction; immune response; microbial metabolism.

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Figures

Fig. 1

Fig. 1

Schematic of the bacterial metabolic pathways that influence the host immune system. Metabolism of indigestible carbohydrates, primary bile acids, phytoestrogens, and tryptophan by commensal gut bacteria results in production of metabolites such as short-chain fatty acids (SCFAs), secondary bile acids, phytoestrogen metabolites, and indoles/indole derivatives, respectively. These bacterial metabolites exert anti-inflammatory effects on mucosal immune cells, and has been demonstrated in vitro and in vivo. Bacterial metabolites can 1) promote barrier function and epithelial integrity; 2) induce tolerogenic dendritic cells (DCs), which trigger the polarization of CD4+ T cells into interleukin (IL)-10 and/or transforming growth factor (TGF)-β-producing FoxP3+ regulatory T cells (Tregs); and 3) directly induce IL-10 and/or TGF-β producing FoxP3+ Tregs. This tolerogenic intestinal environment may influence the peripheral immune system, and thereby lead to protection against and/or amelioration of experimental autoimmune encephalomyelitis (EAE)/multiple sclerosis (MS). IEC = intestinal epithelial cell

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