Disease ⇒ Multiple Sclerosis {40000102}

Record Keys


Type:
Disease
Parent:[  ]
Definition:
Multiple Sclerosis

Details


Initialisation date:
2020-09-06
Other Terms:
MS

Links


Meta Information


MedDra ID:
10028245
MedDra Level:
pt
ICD:[  ]
Category:
Neurology
Zone:[  ]
Mechanism:[  ]

Notes:


- Mice colonized with B fragilis and Polysaccharide A molecule become resistant to experimental autoimmune encephalitis. (1)

- B. fragilis was able to persist in the gut when added to the IgA-producing mice, but never got established in the guts of the IgA-deficient mice, the team reports.
- IgA caused the microbes to clump together along the gut lining and penetrate the protective mucus layer, allowing them to cozy right up to the gut NULLs cells. Without IgA, the microbes fail to permanently colonize the gut. (2)

- C. kefyr suppressed EAE by modifying microflora.
- Transfer of intestinal microflora of C. kefyr-treated mice reproduced increased Lactobacillales and decreased Bacteroides/Prevotella ratio and ameliorated EAE.(3)

- Because ampicillin was the only antibiotic that reduced symptoms in the mouse model, the researchers looked for microbiota that were almost completely deleted specifically in the ampicillin-treated mice. They found only one such bacteria, a new strain called OTU0002, which genome sequencing indicated was probably a newly isolated bacterium of the Erysipelotrichaceae family. Interestingly, the team found bacteria of the same family that are closely related to OTU0002, in other mammals, including humans.
- EAE symptoms in mice co-colonized with L. reuteri and OTU0002 were more severe than those in OTU0002-only mice, and were just as severe as those in the original model mice, indicating that these two bacteria worked together produced far more devastating results. (4)

- A strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. (5)

-Protein expressed by Lactobacillus reuteri does resemble a region of MOG, and when tested, it weakly activated MOG-specific T cells.
-EAE symptoms in mice co-colonized with L. reuteri and OTU0002 were more severe than those in OTU0002-only mice, and were just as severe as those in the original model mice, indicating that these two bacteria worked together produced far more devastating results. (6)

Methanobrevibacteriaceae
- activates the immune system
- immunoproliferative properties that drive inflammation
- Methanobrevibacter was seven times greater in patients with MS than in the control group, but not every MS patient had the bacteria (7)

- An increase in Archaea (Methanobrevibacteriaceae) in MS vs. controls (p < 0.00001 by 454 sequencing).
- Archaea are in a kingdom separate from bacteria and eukaryotes and in the human gut are dominated by Methanobrevibacter smithii, which make up 10% of colonic anaerobes in the gut. (8)

- Lipid 654 , a unique bacterial lipodipeptide, that is produced by a number of commensal Bacteroidetes is found in significantly lower levels in serum from MS patients versus healthy individuals.
- it is unknown whether Lipid 654 is secreted by these organisms or is released upon death or phagocytosis of the bacteria.
- Lipid 654 chronically enters the systemic circulation from commensal bacteria residing in the GI tract and oral cavity, and serves as an immunoregulatory factor normally dampening and regulating immune responses in healthy individuals.
- Lipid 654 is found in significantly lower levels in serum from MS patients versus healthy individuals. (9)

Butyricimonas virosa
- produce butyrate, which is thought to be immunosuppressive.
- Butyricimonas was three times lower in untreated patients with MS than in healthy controls
- Butyricimonas dig butyrate is produced. Butyrate influences the production of regulatory T cells in the ests dietary fiber,gut(?)
- Erysipelotrichaceae plays an important role in bile acid metabolism, which can induce anti-inflammatory properties (?)
- significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA (10)

- Decreased Prevotella levels have been reported in diseases such as type-1-diabetes and autism
- Prevotella histicola can suppress disease in experimental model of MS
- Interestingly, Prevotella is associated with the metabolism of phytoestrogens and plant-derived xenoestrogen > Low estrogen states such as menopause and the postpartum period are clearly associated with increased activity in women with MS > treatment with estrogens can suppress and/or protect animals from disease in an experimental model of human MS (11)

- This module included four ASVs that were nominally linked to a higher risk for relapse, including Blautia massiliensis, Dorea longicatena, Coprococcus comes and a species of the genus Subdoligranulum that researchers described as “unknown.” (12)

- Phylum Euryarchaeota green↑
- Phylum Verrucomicrobia green↑
- Genus Methanobrevibacter green↑ ↑
- Genus Desulfovibrio green↑
- Genus Akkermansia green↑
- Genus Butyricimonas green↓
- Genus Ruminococcaceae green↓
- Genus Bifidobacterium green↑
- Genus Faecalibacterium green↓
- Genus Prevotella green↓
- Species Methanobrevibacter smithii green↑
- Species Akkermansia muciniphila green↑
- Species Butyricimonas virosa green↓ (13)

Shared Reference Notes


  • [1.1
    - IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases.
  • [1.2
    - Two types of inflammatory molecules, known as IL-17A and IL-17F, are involved in the development of MS
  • [1.3] [#Crohn’s disease, #Rheumatoid Arthritis
    - Significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA.
  • [1.4
    - increases in Lactococcus, Mogibacteriaceae, Erysipelotrichaceae Clostridium, and Lachnospiraceae Clostridium and reduced levels Ruminococcaceae. - Increased Butyricicoccus, Akkermansia, and Holdemania were three of the seven taxa consistently predicted in our MS models
  • [1.5
    - Increased #Blautia has also been seen in #Obesity, Alzheimer’s disease, nonalcoholic fatty liver disease, and multiple sclerosis.
  • [1.6
    - Breakdown of the blood brain barrier (BBB) is one of the earliest events seen in MS, which may play an vital role in permitting infiltration of peripheral immune cells. - In the context of MS and EAE, glial dysregulation and disruption of their normal function contributes to demyelination, neuroinflammation and neurodegeneration.
  • - Addition of a single probiotic bacterial species, #Bacteroides fragilis Depending on Polysaccharide A Expression, can ameliorate MS disease through immunomodulation .
  • [1.7] [#Equol] [#Isoflavone diet
  • [1.8
    - #Dimethyl fumarate in MS patient > depletion of some gut microbiota > decreased phenol and indole group metabolites of bacterial origin (e.g. p-cresol-sulfate, indoxyl-sulfate and N-phenylacetylglutamine) > Improved MRI metrics, disability and cognition
  • [1.9
    - Risk of MS increased 32-fold after infection with #EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. - Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after #EBV seroconversion.
  • [#Chronic fatigue syndrome, #Inflamatory bowel disease] - MC/CFS > a reduction of #Faecalibacterium was also found in IBD patients with fatigue (compared to IBD patients without fatigue), , #Cancer-related fatigue (compared to #Cancer patients with low fatigue) and other autoimmune diseases such as MS and #Diabetes Type 1 .
  • [1.11
    - #Saccharomyces and #Aspergillus were over-represented in pwMS. - #Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while #Aspergillus was positively correlated with activated CD16+ dendritic cells in pwMS.
  • [1.12
    - Intermittent #Fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). - IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. - IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells.
  • [1.13
    - Orally administered EDP1867, a gamma-irradiated strain of #Veillonella parvula, rapidly transits through the murine gut without colonization or alteration of the background microbiome flora. - In murine models of inflammatory disease including delayed-type hypersensitivity (DTH), #Atopic Dermatitis, #Psoriasis, and experimental autoimmune encephalomyelitis (EAE), treatment with EDP1867 resulted in significant reduction in inflammation and immunopathology.
  • [1.14] [#Branched-chain amino acids
    - decreased levels of BCAAs in the blood are negative signs linked with abnormal energetic metabolism for MS prognosis.
  • - The enhanced conversion of tryptophan into #kynurenine is associated with MS occurrence and worse outcomes.
  • [1.15] [#Cow’s milk (Dietary Casein)
    - a high percentage of MS patients harbor antibodies to bovine #Casein - antibody cross-reactivity between cow’s milk and CNS antigens can exacerbate demyelination
  • [1.16] [#Short Chain Fatty Acid
    - SCFAs can restore the function of the blood-brain barrier in patients with multiple sclerosis.
  • [1.17] [#Periodontal disease] [#Porphyromonas gingivalis] [#Lipopolysaccharide
    - in periodontitis-diseased tissues, P. gingivalis was present, but not much LPS was evident in tissues. - these bacterial lipids accumulate in structures in blood vessels that can lead to thickening or blockages called atheromas. - in the blood of MS patients, and they found that the bacterial lipid levels were lower in MS patients, a very surprising result. They expected, if anything, that patients with the autoimmune disease would have more lipid present.
  • [1.18
    - Multiple Sclerosis > Certain taxa > expression of immunity-related genes, particularly those associated with dendritic cell maturation, interferon signalling, and NF-kB signalling in circulating T cells and monocytes.
  • - bacterial taxa found to be more abundant in patients with MS increased the inflammatory response both in vitro and in mice monocolonised with those bacteria. - bacterial taxa found to be less abundant in patients were able to stimulate differentiation to anti-inflammatory T cells both in vitro and in monocolonised mice.
  • - Multiple Sclerosis > In the paediatric population, an inverse correlation has been observed between the phylum #Bacteroidetes and Th17 cells (which are associated with autoimmunity)
  • - differences were also observed between treated and untreated MS patients in the abundance of #Prevotella copri, which has previously been suggested to have a protective effect against MS.
  • [1.19
  • [#Alzheimer’s disease, #Parkinson’s Disease] [#Short Chain Fatty Acid] - SCFAs maintain the healthy mitochondrial function and stimulate the maturation of microglia, which consequently suppresses the progression of Neuro-Degenerative Diseases and cognitive decline by regulating inflammation and oxidative stress. - SCFAs functions as a cofactor for the host’s mitochondrial enzymes. - The properties of SCFAs depend on the G-protein coupled receptors (GPCR), histone deacetylases (HDAC) & peroxisome proliferator-activated receptor gamma (PPARγ) and regulatory T cells (Tregs) activation.
  • [1.21] [#Indole, #Tryptophan
    - There are decreased circulating levels of AhR agonists in individuals with multiple sclerosis.
  • [1.22] [#Short Chain Fatty Acid
    - Individual dietary fiber sources have distinct impacts on T cell subsets - The dietary fiber #Guar gum impairs Th1 polarization and alters migratory potential - #Guar gum elevates short-chain fatty acids but does not impact regulatory T cells - #Guar gum supplementation significantly delays autoimmune neuroinflammation
  • [1.23
    - significantly increased proportion of Akkermansia muciniphila, Ruthenibacterium lactatiformans, Hungatella hathewayi, and Eisenbergiella tayi and decreased Faecalibacterium prausnitzii and Blautia species.
  • - The #Phytate degradation pathway was over-represented in untreated MS, while #Pyruvate-producing carbohydrate metabolism pathways were significantly reduced.
  • [1.24] [#Blautia wexlerae, #Erysipelotrichaceae CCMM
    - In both progressive MS and RRMS > increased #Clostridium bolteae, #Ruthenibacterium lactatiformans, and #Akkermansia and decreased #Blautia wexlerae, #Dorea formicigenerans, and #Erysipelotrichaceae CCMM. - Unique to progressive MS, has elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased #Blautia and #Agathobaculum.
  • [1.25
    - MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine.
  • - concentrations of fecal SCFAs (i.e., #Acetate, #Butyrate and #Propionate) were decreased in RRMS patients, compared to healthy controls
  • - Faecalibacteria, #Lachnospiraceae, and #Anaerostipes produce butyrate, which acts via G-protein coupled receptors activation and histone deacetylase inhibition to suppress CNS demyelination, the main pathological feature in MS.
  • [#Bacteroides thetaiotaomicron] [#Meat-based diet] - Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites.
  • - six species are significantly lower in abundance in MS patients than in controls, three of which have known immunomodulatory properties (#Bifidobacterium longum, #Clostridium leptum, #Faecalibacterium prausnitzii)
  • - #Collinsella aerofaciens, #Coprococcus comes , #Phascolarctobacterium succinatutens , #Sutterella wadsworthensis were positively correlated with the EDSS (expanded disability status scale).
  • - #Eubacterium siraeum was negatively correlated with EDSS (expanded disability status scale).
  • - MS patients > reduced abundance of #Prevotella copri, in stools of MS patients
  • - #Prevotella histicola reduces EAE severity by inducing FoxP3+ regulatory T cells and decreasing pro-inflammatory Th1 and Th17 cells in the CNS.
  • - #Propionic acid, but not butyrate and acetate, was significantly reduced in blood and stool in MS patients with all disease subtypes, particular after relapse. - Supplementation of #Propionic acid promoted Treg cell function, and in long-term administration reduced relapse rate, disability and brain atrophy.
  • [#Short Chain Fatty Acid] - Blood SCFAs were significantly decreased in long-term active progressive MS patients.
  • [1.26
  • [1.27] [#Isoflavone diet, #Phytoestrogen-free (phyto-free) diet
    - gut microbiota of MS Patients resembles the gut microbiota of mice raised under a #Phytoestrogen-free (phyto-free) diet in that it lacks #Phytoestrogen-metabolizing bacteria. - the change in diet from one that is ISO to one that is PF reduces beneficial bacteria such as Bifidobacterium species. - isoflavone-rich diet specifically modulates LPS biosynthesis of the gut microbiota imparts an anti-inflammatory response and decreases disease severity
  • [1.28
    - patients with multiple sclerosis (MS), a neuroinflammatory disease, lack gut bacteria that are able to metabolize #Phytoestrogen.
  • [1.29
    - cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages
  • [#Urolithins] - in non-disease-active cases, #Faecalibacterium prausnitzii and #Gordonibacter urolithinfaciens, whose absolute abundance was enriched. - These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin.
  • [#Lipocalin-2] - bacteria thought to be beneficial for inflammatory bowel disease (IBD) such as #Anaerobutyricum, #Blautia, and #Roseburia, were reduced in fecal Lcn-2-high MS patients.
  • [#Lipocalin-2] - decreasing trend in serum #Acetate (a short-chain fatty acid) levels in MS Lcn-2-high patients compared to healthy donors (HDs). - a decrease in the relative abundance of #Blautia massiliensis was significantly associated with a reduction of #Acetate in the serum of MS patients.
  • - fecal #Lipocalin-2 (Lcn-2), a biomarker of intestinal inflammation, was significantly elevated and predominantly produced by the gut-infiltrating neutrophils. - The elevation of fecal Lcn-2 levels correlated with reduced bacterial diversity and increased levels of other intestinal inflammation markers including neutrophil elastase and #Calprotectin.
  • [1.31
    - definitive association between an increased risk of multiple sclerosis and prior infection with the Epstein-Barr virus (#EBV).
  • [1.32] [#Bile Salt, #Short Chain Fatty Acid
    - MS > the absence of AHR, changes the gut microenvironment composition to generate metabolites that impact T cell viability, such as bile salts and short chain fatty acids.
  • [1.33] [#Alzheimer’s disease, #Parkinson’s Disease
  • [1.34] [#Alzheimer’s disease, #Amyotrophic lateral sclerosis
    - ALS appeared to be less associated with microbial dysbiosis compared to MS and AD, with only one microbe genus, #Methanobrevibacter and #Ruminococcaceae being commonly present under elevated conditions, respectively.
  • - The gut microbial dysbiosis in MS leads to the reduction of microbes which can elicit an anti-inflammatory response through immune cells like T regulatory cells, regulatory B cells and Interleukin 10 (IL-10) in host
  • [#Parkinson’s Disease] - microbial dysbiosis showed the highest similarity between the two diseases, MS and PD
  • - MS patients exhibited reduced serum and fecal concentrations of #Propionic acid. - administration of #Propionic acid in MS patients showed increased functionality of competent regulatory T cells and reduced brain atrophy
  • [1.35] [#Inflamatory bowel disease] [#Akkermansia muciniphila] [#Antibiotic Therapy
    - Conditions like inflammatory bowel disease (IBD), #Salmonella typhimurium infection or post-antibiotic reconstitution may not benefit from #Akkermansia supplementation. - using #Akkermansia in patients with endocrine and gynecological disorders—such as #Polycystic ovary syndrome (PCOS) or #Endometriosis—that have a higher risk of developing IBD, should be critically evaluated. - the gut microbiota of patients suffering from #Parkinson’s Disease or multiple sclerosis exhibits a characteristic signature of #Akkermansia municiphila abundance.
  • [1.36] [#Alzheimer’s disease] [#Enterobacteriaceae bacterium
    - AD elders were also depleted in #Adlercreutzia equolifaciens, an #Equol-producing bacterium, which has beneficial effects in reducing experimental cutaneous inflammation in mice and the loss of which has been associated with the neurodegenerative disorder multiple sclerosis.
  • [1.37
    - In MS, the gut mycobiome differs from that of healthy individuals, with enrichment of #Candida and #Epicoccum as well as a lower relative abundance of #Saccharomyces.
  • [1.38] [#Dorea formicigenerans
    - D. formicigenerans degrades mucin and may play an inflammatory role in patients with multiple sclerosis
  • [1.39
    - In metabolic diseases such as #Obesity, chronically elevated levels of #Leptin are observed, which can induce the production of proinflammatory molecules and impair immune self-tolerance, predisposing to develop conditions such as #Rheumatoid Arthritis, inflammatory bowel disease, multiple sclerosis, and others
  • - #Lactate, produced by activated Dendritic cells (DCs) and other immune cells, boosts the expression of NDUFA4L2 through a mechanism mediated by hypoxia-inducible factor 1α (HIF-1α). - NDUFA4L2 limits the production of mitochondrial #Reactive Oxygen Species that activate XBP1-driven transcriptional modules in DCs that are involved in the control of pathogenic autoimmune T cells. - a #Probiotic that produces #Lactate and suppresses T cell autoimmunity through the activation of HIF-1α–NDUFA4L2 signalling in DCs.
  • [1.41
    - Deficit in dietary #AHR ligands increases the severity of inflammation in the central nervous system, as evidenced in the experimental autoimmune encephalomyelitis (EAE) model
  • [1.42] [#kynurenic acid, #kynurenine
    - the small-intestinal microbes in EAE mice enhanced the KYN pathway, resulting in increased KYNA in the SI; - increased KYNA contributed to the accumulation of Th17-inducing GPR35+ Ly6C+ macrophages in the SI of EAE mice before inflammation in the SC; - microbiota-induced Th17 cells were not retained in the intestines and migrated toward the SC to induce EAE.
  • [1.43
    - Individuals with relapsing-remitting MS have an abundance of #Mycoplasma, #Pseudomonas, #Faecalibacterium, #Haemophilus, #Anaerostipes, #Blautia, and #Dorea, while #Bacteroides, #Prevotella, #Parabacteroides, and #Adlercreutzia are relatively less common.
  • - #Children with MS exhibit low levels of #Lachnospiraceae and #Ruminococcaceae and significant levels of #Desulfovibrionaceae members
  • [1.44
    - both low and high doses of #Curcumin decreased the progression of EAE.
  • [1.45] [#High Fat Diet
    - MS > mice on a high-fat diet showed enrichment of bacteria from the #Desulfovibrionaceae family, specifically #Desulfovibrio piger and #Bilophila wadsworthia. - high-fat diet-induced #Obesity increased EAE disease severity in animal models of MS
  • [#Estrogen, #Phytoestrogen] - Estrogens have also been shown to possess immunomodulatory properties and ameliorate MS during #Pregnancy
  • - Several gut bacteria lacking in MS such as #Prevotella, #Parabacteroides, #Adlercreutzia, and #Bifidobacterium can metabolize dietary #Phytoestrogen.
  • - Ms > The clinically nonactive (nonrelapsing) patients showed an enrichment of #Faecalibacterium prausnitzii, #Gordonibacter urolithinfaciens, #Anaerostipes hadrus, #Gemmiger formicilis, and #Roseburia inulinivorans compared to clinically active patients
  • - gut resident #Fungi (mycobiome) are also modulated in MS characterized by a reduced abundance of #Saccharomyces
  • - MS > bacterial species more abundant in clinically active treatment-naïve cases were positively associated with circulating levels of pro-inflammatory cytokines #IL-22, #IL-17A, IFN-β, IL-33, and TNF-α.
  • [#Isoflavone] - mice on a diet with isoflavones (a type of #Phytoestrogen) are protected from EAE> depended on the presence of gut microbiota as antibiotic depletion of microbiota abrogated the disease protective effect, and supplementation with #Phytoestrogen metabolizing bacteria restored disease protective function.
  • - Ms > The clinically active group showed significant enrichment of #Methanobrevibacter smithii and #Victivallis vadensis.
  • - MS patients lack gut bacteria capable of metabolizing dietary #Phytoestrogen
  • [1.46] [#Alzheimer’s disease, #Amyotrophic lateral sclerosis, #Parkinson’s Disease
    - #Ferulic acid (FA), which occurs naturally as the feruloylated #Sugar ester in grains, fruits, and vegetables, is critical for combating #Oxidative stress and alleviating neurodegenerative diseases resulting from free radical-generated protein aggregates in brain cells. - #Ferulic acid esterases (FAE) of the gut microbiota are critical enzymes that facilitate FA release from feruloylated #Sugar ester conjugates and influence systemic health.
  • [1.47
    - #Tryptamine is a neuromodulator with antioxidant characteristics that is produced when commensal bacteria break down #Tryptophan. - Deficits in #Tryptophan-derived #Neurotransmitters like #Serotonin and #Melatonin, which are both essential for #Sleep, are frequently linked to MS comorbidities, including #Depression
  • - Particularly #Propionate supplementation has shown immunomodulatory effects in people, lowering Th17 cells and raising T reg. - In MS patients, long-term #Propionate supplementation lowered relapse rates, stabilized disability, and stopped brain shrinkage

References Notes


  • [1.3
  • [1.64
  • [1.65

Common References


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