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Advanced Neurologyurology
Advanced Ne The role of gut in multiple sclerosis

Intestinal microflora has recently emerged as an 2. The gut microbes in the pathogenesis
important environmental component that may provide and progression of MS
important clues to the progression of inflammation and
the development of MS. An abnormal intestinal flora was 2.1. Preclinical evidence from the EAE model
found to be differentially abundant among MS patients Segmented filamentous bacteria (SFB) are important
compared with healthy controls (HCs), though with little communicators for the differentiation of Th17 cells [19] .
consistency in the bacterial taxa [7-10] . In MS patients, the It was demonstrated that actively generated EAE is
composition of the intestinal flora is aberrant, including a reduced in GF mice yet is recovered through SFB gut
rise in potentially pathogenic microbes and a reduction in colonization [20] . In addition, Berer et al. showed that
the number of helpful bacteria, according to metagenomic EAE-resistant GF animals spontaneously acquire
research [11-13] . Another study on how the intestinal EAE without any treatment with adjuvant or pertussis
microbiota affects people with MS was done by Kadowaki toxin following recolonization with native microbes
et al. They discovered that the connections between the T or a variety of SFB utilizing a T-cell receptor (TCR)
cell C-C chemokine receptor type 9 (CCR9) and its ligand transgenic mouse model of EAE [21] . Notably, the majority
C-C chemokine ligand 25 (CCL25) were affected by the of SFB-induced Th17 cells respond to SFB antigens,
gut microbiota. The small intestine epithelium is involved emphasizing the importance of microbic antigens
in this interaction, which affects T cell growth and during the activation of effector T cells within the gut [22] .
immunity. CCR9 function was shown to be diminished In fact, after SFB colonization, SFB-specific CD4 T
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in MS patients. CD4 T cells increased the expression cells of mesenteric lymph nodes (MLNs) are prepared
+
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of CCR9 on T cells. The number of CCR9 memory T to develop into Th17 cells [23] . Through processes of
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(Tm) cells in peripheral blood was reduced as a result bystander activation or cross-reactivity between SFB
of blocking the CCR9-CCL25 interaction. To ascertain and as of yet uncharacterized CNS antigens, SFB may
if the gut microbiota has an impact on CCR9 Tm cells, stimulate T lymphocytes with CNS reactivity. SFB-
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CD4 Tm cells from peripheral blood of germ-free (GF) specific Th17 cells may either recirculate to the CNS
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mice conditions have been examined. In GF mice, the after migrating to intestinal mucosa following priming
number of CCR9 Tm cells decreased. The researchers in MLNs or might straight enter the CNS through the
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also gave wild-type mice short-term antibiotic therapy systemic circulation. Intriguingly, it has recently been
after inducing EAE in them. Treatment with antibiotics discovered that gut nociceptor neurons, which are often
increased the number of CCR9 Tm cells and significantly linked to protective reflexes, regulate SFB levels. This
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reduced the severity of EAE . This finding supports the suggests that their activity might obliquely govern the
[14]
possibility that gut dysbiosis, through affecting the gut- development of CNS-reactive Th17 cells [24] .
systemic immunological axis, contributes to the genesis
of MS. Furthermore, immunoglobulin A (IgA) protects It is worth noting that the impacts of MS on the
the mucosal epithelium from invading pathogens, composition and variety of gut microbes differed in
toxins, and food-derived antigens but also regulates gut animal models. Omura et al. created an MS model using
microbial composition . The effectiveness of anti-B Theiler’s murine encephalomyelitis virus (TMEV)-
[15]
treatments and novel genetic research has highlighted infected SJL/J mice and collected feces from TMEV mice
the significance that B cells regulate neuroinflammation on day 4 (pre-onset phase), day 7 (acute phase), and day
in MS [16,17] . Plasma cells of secretory IgA (IgA PC)’s 35 (chronic phase). According to RNA sequencing, the
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gut origins have been shown in the EAE mouse model, abundance of individual bacteria genera Marvinbryantia
and they decreased inflammation of the nervous system increased on days 7 and 35, while Coprococcus increased
under an IL-10-dependent way, underscoring the growing on day 35. However, neither the microbial biodiversity nor
[25]
significance of mucosal immune deficiency in MS. IgA the overall microbiota pattern was altered . Moreover,
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PC gut-derived intraepithelial lymphocytes suppressed after the EAE induction, the gut microbiota composition
neuroinflammation, prevented EAE, and decreased the of EAE-resistant Albino Oxford rats was more stable,
number of CD4 T cells that cause granulocyte-macrophage whereas the gut bacterial diversity of EAE-susceptible
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colony-stimulating factor as they moved from the gut Dark Agouti rats was higher . Constipation-induced
[26]
to the periphery and subsequently to the inflamed CNS, intestinal dysbiosis worsens EAE symptoms in C57BL/6
which patients with MS have seen a comparable decrease mice while also reducing the abundance and diversity of
[27]
in IgA-bound fecal bacteria following relapse . In all, the intestinal microbiota . These contradictory results
[18]
emerging evidence established a critical link between the hint indirectly at the potential influence of mice species
gut and MS. on gut microbes.

Volume 2 Issue 3 (2023) 2 https://doi.org/10.36922/an.413