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Advanced Neurology The role of gut in multiple sclerosis

also discovered that MS patients have a higher proportion The start of EAE in mice is paradoxically prevented by
of butyrate and propionate levels that are compared to HCs a complete lack of dietary tryptophan before vaccination
and that both butyrate and valerate are positively correlated due to the microbiota-dependent harm to brain T
[59]
with pro-inflammatory cytokines . These findings may cells [64,65] . However, mice fed with a control diet started
suggest a labyrinthine function of SCFAs in the regulation to show a reduction in EAE symptoms, whereas clinical
of CNS autoimmune inflammation. disease worsens if dietary tryptophan is withdrawn after
[65]
the onset of EAE . Another study showed that IFN-β
3.2. Tryptophan causes the AhR expression of astrocytes, which might lead
Tryptophan is a naturally occurring monoamine alkaloid to a therapeutic IFN-β’s role in MS through increasing glial
with a function as an agonist of the aromatic hydrocarbon cell responsiveness to anti-inflammatory AhR ligands. In
receptor and is also produced by gut microbiota metabolism. addition, the AhR ligands indoxyl 3-sulfate, IPA, and IAld
The metabolic products of tryptophan include indole-3- all alleviated EAE via AhR signaling and restricted astrocyte
lactic acid (ILA), indole-3-acetic acid (IAA), and indole- production of IL-6, tumor necrosis factor (TNF)-α, CCL2,
[68]
3-carboxaldehyde (IAld). Furthermore, other metabolic and inducible nitric oxide synthase .
products (kynurenine, kynurenic acid, and xanthurenic 3.3. Phytoestrogens
acid) act as ligands for the aryl hydrocarbon receptor (AhR)
and can have immune- and neuro-modulatory impacts. Phytoestrogens are dietary substances generated from plants
that share structural similarities with 17-estradiol. Given
When compared to HCs, serum tryptophan this, phytoestrogens may also affect immune function in
concentrations were lower and kynurenine levels were MS [69,70] . Prevotella, Parabacteroides, Adlercreutzia, Slackia,
higher in MS patients, indicating that tryptophan and Lactobacillus, which metabolize phytoestrogens as well
metabolism may be disturbed in this condition . Dietary as improve bioavailability, diminished among MS patients,
[60]
tryptophan shortage exacerbated the clinical course of hence demonstrating that phytoestrogen is linked to the
EAE in mice. When tryptophan was added back into the etiology of MS [71-73] . Recently, an eating plan that contains
diet, it alleviated the condition in wild-type mice but not in phytoestrogen decreased EAE disease from a manner that
AhR mice . The analysis of tryptophan derivatives now depended on phytoestrogen-metabolizing bacteria. In
[61]
-/-
includes AhR ligands as a result of recent investigations. addition, it is demonstrated that mice given this diet and
Elevated blood indole-3-propionic acid (IPA) and IAA devoid of phytoestrogens had intestinal flora compositions
concentrations in children with MS are linked to higher that were strikingly comparable to those of MS patients.
rates of cognitive processing and less severe illness . In These findings imply that commensal bacterially generated
[62]
addition, a lower risk of recurrence was linked to the fecal food phytoestrogen metabolites may have an impact on
microbiota’s enrichment of tryptophan catabolism-related CNS autoimmunity.
genes. This is supported by the finding that AhR ligand
levels in the blood are lower in RRMS patients compared Isoflavones are phytoestrogens that are only metabolized
to HCs, exception for patients with benign disease (long- by the human body via gut microbes. It was discovered that
standing diagnosis, but mild clinical symptoms) and those the number of bacteria capable of metabolizing isoflavones
who are actively relapsing, where they might be upregulated was low in MS patients, and further research revealed
in an anti-inflammatory feedback loop . that isoflavone diet mice had an altered gut microbial
[63]
composition as well as an anti-inflammatory phenotype
Laquinimod, a synthetic indole-containing substance, that inhibited EAE [37,38,74] .
reduced EAE by activating AhR-dependent signaling in
astrocytes. Laquinimod clinical trials, however, have had 4. Therapeutic implications for microbiota
conflicting outcomes [64,65] . Laquinimod did not significantly in MS
slow the course of RRMS despite a considerable reduction
in brain shrinkage (Clinical Trial NCT01707992) . 4.1. Probiotics
[66]
When Lactobacillus murinus and Lactobacillus reuteri Much research in recent years has focused on
are administered as probiotics, fecal levels of tryptophan probiotics to restore the balance of the gut microbiota.
metabolites such as ILA, IAA, and IAld are raised and It is thought that these live microorganisms work by
ameliorate EAE. Although this impact was not investigated altering the gut microbes to encourage intestinal barrier
with the other metabolites, it was hypothesized that ILA integrity as well as the differentiation and activation of
would have a protective role by lowering Th17 polarization immunoregulatory cell subsets over inflammatory cell
and IL-17A production from myelin oligodendrocyte subsets [75,76] . Oral probiotics improved gut microbiota
glycoprotein peptide (MOG)-reactive T cells . diversity by increasing the abundance of many species,
[67]

Volume 2 Issue 3 (2023) 5 https://doi.org/10.36922/an.413