An increase of multiple sclerosis (MS) incidence has been reported during the last decade, and this may be connected to environmental factors. This review article aims to encapsulate the current advances targeting the study of the gut–brain axis, which mediates the communication between the central nervous system and the gut microbiome. Clinical data arising from many research studies, which have assessed the effects of administered disease-modifying treatments in MS patients to the gut microbiome, are also recapitulated.

In the Russian Federation, multiple sclerosis prevalence rates vary from 10 to 80 cases per 100,000, depending on region and the nationality of the population. The main characteristics of multiple sclerosis epidemiology in the XX century in this big territory are: (1) steady increase in multiple sclerosis prevalence and incidence rates, maybe because of better diagnosis and treatment, but also changes in environmental/epigenetic risk profile and/or lifestyle factors; (2) increase of the female to male ratio, increase in multiple sclerosis incidence mainly in females; (3) appearance and increasing frequency of multiple sclerosis in ethnic groups, previously free of multiple sclerosis (Northern Tribes, Yakuts and others). The latest data show that in European Russia, the multiple sclerosis prevalence varies from 30 to 80 cases, in Siberia—from 20 to 70 cases, with steady increases, especially in women.

Glatiramer acetate (GA) is approved for the treatment of multiple sclerosis (MS). However, the mechanism of action of GA in MS is still unclear. In particular, it is not known whether GA can modulate the pro-inflammatory Th17-type immune response in MS. We investigated the effects of original GA (Copaxone^®, Teva, Israel) and generic GA (Timexone^®, Biocad, Russia) on Th17- and Th1-type cytokine production in vitro in 25 patients with relapsing-remitting MS and 25 healthy subjects. Both original and generic GA at concentrations 50–200 μg/ml dose-dependently inhibited interleukin-17 and interferon-γ production by anti-CD3/anti-CD28-activated peripheral blood mononuclear cells from MS patients and healthy subjects. This effect of GA was reproduced using purified CD4⁺ T cells, suggesting that GA can directly modulate the functions of Th17 and Th1 cells. At high concentrations (100–200 μg/ml), GA also suppressed the production of Th17-differentiation cytokines (interleukin-1β and interleukin-6) by lipopolysaccharide (LPS)-activated dendritic cells (DCs). These GA/LPS-treated DCs induced lower interleukin-17 and interferon-γ production by autologous CD4⁺ T cells compared to LPS-treated DCs. These data suggest that GA can inhibit Th17-immune response and that this inhibitory effect is preferentially exercised by direct influence of GA on T cells. We also demonstrate a comparable ability of original and generic GA to modulate pro-inflammatory cytokine production.

Endothelial dysfunction is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and the prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is a dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and the induction of the apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in MS pathogenesis.