Objective: to study the role of the human gut microbiome in the mechanisms of multiple sclerosis (MS) development and in the formation of response to immunomodulatory therapy. Material and methods. The study included 100 people – 80 patients with MS, 65 of whom had relapsing-remitting MS (RRMS) and 15 had primary-progressive MS (PPMS), all before being prescribed glucocorticoid therapy, as well as 20 healthy people of the same age. The gut microbiome was studied using 16S rRNA gene analysis. The influence of gender, duration and severity of MS, therapy received, the presence of a risk factor for MS exacerbation (smoking), and the presence of a predisposing factor in the genotype (DR2 (15) haplotype) were assessed. Results. For MS, regardless of gender, disease duration, type of course, treatment received, and other clinical and demographic characteristics, there is generally an increase in the content of rare forms of bacteria of the Verrucomicrobia type and related classes, orders, and families, as well as a decrease in the level of butyrate-producing bacteria of the genus Roseburia, which has an anti-inflammatory effect. The microbiome of male MS patients is more enriched with microorganisms, as in women in the control group, which can be regarded as one of the compensatory anti-inflammatory mechanisms that reduce the spread of MS in men. In cases of short-term MS, the gut microbiome was dominated by bacteria of the classes Erysipelotrichia, Verrucomicrobiae and Deltaproteobacteria, with the latter two being characteristic of all types of MS, indicating their role in the formation of a predisposition to MS; As the duration of MS increased, the content of bacteria of the genus Phascolarctobacterium increased, while the decrease in the level of bacteria of the genus Roseburia and OTU₈25 (Roseburiaᵢntestinalis), typical for MS, did not depend on the duration of MS. As the severity of MS increased on the EDSS scale, a predominance of rare forms of the class Verrucomicrobiae, family Verrucomicrobiaceae, was noted. In severe patients with EDSS ≥4. 5 points, a predominance of bacteria of the class uncBacteroidetes was noted. In PPMS, as a more unfavourable type of MS course, the levels of bacteria of the Desulfovibrionaceae fam- ily, Akkermansia genus and OTU₃0 (Akkermansiaₘuciniphila) were significantly increased (both compared to PPMS and compared to the control), and the level of OTU₈25 (Roseburiaᵢntestinalis) are significantly increased (compared to both PPMS and the control group), while the level of OTU₈25 (Roseburiaᵢntestinalis) is even lower than in typical relapsing MS, indicating a more unfavourable course of MS with a predominance of the neurodegenerative process. During exacerbation of PPMS, a statistically significant increase in the presence of Proteobacteria and other classes, families and genera of bacteria associated with inflammation, indicating the involvement of the microbiome not only in the formation of predisposition, but also in a short-term increase in the activity of autoimmune inflammation, leading to an exacerbation of the pathological process in brain tissue. Many differences between the gut microbiome of MS patients and that of the control group were most significant in the group of smokers. An increase in the presence of Verrucomicrobiaceae bacteria in the gut microbiome in MS was most noticeable in carriers of the HLA-DRB1-2 (15) genetic marker, which increases the risk of developing MS. High-dose IFN therapy may alter the composition of the gut microbiome, possibly due to the growth of anti-inflammatory microbiome, partic- ularly Holdemanella and Megasphaera, as well as butyrate-producing bacteria OTU₃3 (uncLachnospiraceae). Conclusion. The gut microbiome plays an important role in shaping the course and response to treatment in MS.
Kozhieva et al. (Mon,) studied this question.