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Advanced Neurology The role of gut in multiple sclerosis

can restrain EAE symptoms in HLA class-II transgenic Among them, butyrate increases cellular metabolism and
model. P. histicola restrains disease by the alteration of improves the memory capacity of activated CD8 T cells .
+
[47]
systemic immune responses, leading to a decrease in pro- It is worth noting that SCFAs can move across the BBB
inflammatory Th1 and Th17 cells as well as a rise in the and there are functional SCFA receptors in the CNS [48,49] .
frequencies of CD4 FoxP3 regulatory T cells, tolerogenic It is also notable that some SCFA-producing bacteria,
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[50]
DC, and suppressive macrophage . These findings point including A. muciniphila, Roseburia inulinivorans ,
[43]
to functional relationships between variations in certain Butyricimonas , and Faecalibacterium prausnitzii , have
[35]
[51]
gut bacteria and a change toward a pro-inflammatory been characterized.
T-cell profile that may amplify or sustain autoimmune Acetate, propionate, and butyrate concentrations in
responses, perhaps discovering a previously unidentified feces and blood samples are lower in MS patients than in
environmental factor to MS pathogenesis. HCs, possibly pointing to a protective role for SCFAs in
2.2.4. Other evidence MS [41,52-54] . Notably, compared to healthy people, secondary
progressive MS patients had lower blood levels of acetate,
Although immunological markers (such as Th2, Th17, and propionate, and butyrate. The feces sample of RRMS
Treg) did not change between cases and controls in research patients likewise revealed identical findings, indicating
of 24 kids (15 in relapsing remission and 9 in controls), that these changes happen independently of the disease
gut microbiota associations did. Species richness and types [52,54] . Decreased relative abundance of recognized
Th17 showed a positive correlation for relapsing remission SCFA-producers among the MS microbes, such as
patients. Bacteroidetes had a negative correlation with Roseburia, Coprococcus, Blautia, Faecalibacterium, Dorea,
Th17 in relapsing remission patients, whereas Fusobacteria Butyricicoccus, and Clostridium XIVb, is correlated with
had a positive correlation with Tregs in control patients . decreases in fecal SCFAs [41,55] .
[13]
Another study that included 18 pediatric RRMS cases and SCFAs have implications for MS disease. Serum caproic
17 controls discovered that, in comparison to controls, acid (CA) concentrations increased in MS patients as
MS cases had a significant depletion in Lachnospiraceae butyrate and acetate concentrations decreased. CA was
and Ruminococcaceae as well as enrichment in members also found to be positively associated with CD4 IFN-ɣ
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of the Desulfovibrionaceae (Bilophila, Desulfovibrio, and T cells . Similarly, another study discovered that
[41]
Christensenellaceae). Microbial genes with expression acetate concentration decreased in MS patients, which
higher in MS than in control are involved in glutathione was associated with a negative relationship with the pro-
metabolism, and this result remains the same regardless inflammatory biomarker IFN. In addition, it decreased
of the administration of immunomodulatory drugs . the count of effector T cells in the intestine and increased
[9]
Additional studies have shown that a lower abundance the release of IL-10 by regulatory B cells, which improved
of butyrate-producing microbes, such as Butyricicoccus EAE .
[56]
desmolans and Odoribacter, is linked to a higher risk of MS
disease recurrence among children . Current studies on propionic acid confirm that
[44]
it can improve the severity of MS. With propionate
3. Microbial metabolites in the supplementation, the number of peripheral Tregs and
pathogenesis of MS their ability to inhibit MS symptoms ex vivo and in vitro
were found to increase with propionic acid in a way that
3.1. SCFAs was IL-10-dependent . Furthermore, Tregs treated
[53]
With chain lengths ranging from one to six carbon with propionate were transferred to EAE mice to lessen
atoms, SCFAs are the primary component of dietary fiber the severity of the illness. Last but not least, propionate
fermentation in the colon. Butyrate, acetate, and propionate also raises the quantity of Treg in the spleen and spinal
[57]
are the most common. SCFA helps to keep the intestinal cord . According to these findings, propionate reduces
barrier intact, and butyrate, in particular, improves CNS autoimmunity by raising the number of Treg cells
intestinal barrier function by regulating the expression of throughout the body, including the CNS, where they are
tight junction proteins . Intracellular butyrate, propionate, likely to suppress continuing inflammation.
[45]
and acetate inhibit histone deacetylases (HDACs) activity Notably, Th17 cells treated with acetate exacerbated the
and promote histone hyperacetylation; SCFAs appear to EAE progression. As a result, this might tip the immune
inhibit monocyte, macrophage, and DC maturation by response in favor of a Th17 response . Surprisingly,
[52]
suppressing HDACs, reduce pro-inflammatory cytokine elevated levels of acetate were found in the plasma of MS
production, and promote T cell differentiation into patients and were connected to higher numbers of CD8
+
Th1 cells, Th17 cells, IL-10 T cells, as well as Treg cells . IL-17 T cells and greater neurological impairment . It was
[46]
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[58]
Volume 2 Issue 3 (2023) 4 https://doi.org/10.36922/an.413