Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

Ward J van den Hoogen, Jon D Laman, Bert A 't Hart, Ward J van den Hoogen, Jon D Laman, Bert A 't Hart

Abstract

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research.

Keywords: Food; autoimmunity; fecal transplant; gut microbiome; immunomodulation; prebiotic; probiotic.

Figures

Figure 1
Figure 1
Immune cells involved in the pathology of early MS. Immune cells infiltrate the CNS and are reactivated by APC. The infiltrating T cells produce pro-inflammatory cytokines, which increases immune cell infiltration. The inflammatory milieu also activates microglia, which produce pro-inflammatory mediators and elicit demyelination and axonal loss. Autoantibodies produced by B cells cause damage to myelin through complement-mediated cytotoxicity and macrophage-mediated cytopathic reactions. As the disease progresses, immune cells accumulate in perivascular spaces. ODC, oligodendrocyte; MAIT, mucosa-associated invariant T cells; APC, antigen-presenting cells; CNS, central nervous system; MS, multiple sclerosis. The figure has been inspired by: Fugger et al., Grigoriadis et al., and Goverman (2, 4, 10).
Figure 2
Figure 2
Immune cells involved in the pathology of late MS. Immune cell migration from the periphery into the CNS subsides, but chronic inflammation of the CNS still takes place. Chronic CNS inflammation is associated with tertiary lymphoid-like structures in perivascular spaces and dysfunctional astrocytes and microglia. Microglia activation promotes astrocyte production of CCL2 and GM-CSF, which recruits and activates more microglia. Astrocytes inhibit remyelination, and both microglia and astrocytes produce pro-inflammatory mediators that are neurotoxic and contribute to gradual neurodegeneration. FDC, follicular dendritic cells; ODC, oligodendrocyte; CNS, central nervous system; MS, multiple sclerosis. The figure has been inspired by: Fugger et al. and Goverman (2, 10).
Figure 3
Figure 3
Factors that determine gut microbiota composition. The composition of gut microbiota is influenced by multiple factors, such as diet and host genotype. Within the gut, ecological processes such as selection and evolution take place. The use of antibiotics reduces the numbers and diversity of gut microbiota. The figure has been modified after: Walter and Donaldson et al. (14, 15).
Figure 4
Figure 4
Interactions between members of the gut microbiota and the immune system. Bacteriophages can infect and lyse bacteria or undergo a lysogenic cycle in which they stay dormant inside bacteria. During this process, gene segments may be transmitted which influences the fitness of the bacteria. Bacteria protect themselves from phage infection by CRISPR. Bacteria may cause a pro- and anti-inflammatory effect dependent on the bacterial species. Anti-inflammatory effects include the induction of Treg cells and the reduction of iNKT cells. Pro-inflammatory effects include induction of Th1, Th17, IgA producing B cells and stimulation of IL-22 production by ILC, which increases AMP production. These immune cells and the mucus layer protect the epithelial cells from being infected by bacteria. In addition, phages limit bacteria–epithelial adhesion by binding to the mucus layer. The effects of the gut immune system on phages remain largely unknown. SFB, segmented filamentous bacteria; AMP, antimicrobial peptides; iNKT, invariant natural killer T; ILC, innate lymphoid cells; IEL, intraepithelial lymphocytes; DC, dendritic cell; CRISPR, clustered regularly interspaced short palindromic repeats. The figure has been inspired by: Glenn and Mowry (13).
Figure 5
Figure 5
Similarities and differences in gut microbiota of MS patients and healthy controls. Eight studies investigating almost 250 patient fecal samples for differences in microbiota composition were analyzed. Many species were shown differently present. Only differences that have been reproduced by at least one other study are included in this figure. The gut microbiota of both MS patients and healthy controls are dominated by bacteria from the phyla Firmicutes and Bacteroidetes and their species richness does not differ. MS patients may have increased Methanobrevibacter and Enterobacteriaceae, but reduced Faecalibacterium prausnitzii and SCFA producing bacteria. SCFA, short-chain fatty acids; MS, multiple sclerosis.

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Source: PubMed

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