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Disease ⇒ Multiple Sclerosis {40000102}

Record Keys


Type:
Disease
Definition:
Multiple Sclerosis
Parent:[  ]

Details


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

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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)

References Notes


Shared Reference Notes


  • [1.25
    - 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.
  • [1.26
    - Two types of inflammatory molecules, known as IL-17A and IL-17F, are involved in the development of MS
  • [1.27
    - 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
  • [1.28
    - 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 .
  • [1.20] [#Equol] [#Isoflavone diet
  • [1.19
    - #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
  • [1.11
    - 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.
  • [1.29] [#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 .
  • [1.30
    - #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.
  • [1.31
    - 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.
  • [1.32
    - 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.
  • [1.21
    - 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.
  • [1.18] [#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
  • [1.33] [#Short Chain Fatty Acid
    - SCFAs can restore the function of the blood-brain barrier in patients with multiple sclerosis.
  • [1.34] [#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.
  • [1.7
    - 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.
  • [1.36] [#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.
  • [1.37] [#Indole, #Tryptophan
    - There are decreased circulating levels of AhR agonists in individuals with multiple sclerosis.

Common References