Link Between Gut Flora and Multiple Sclerosis Discovered

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frodo
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Link Between Gut Flora and Multiple Sclerosis Discovered

Post by frodo » Thu Oct 18, 2018 4:04 am

Link Between Gut Flora and Multiple Sclerosis Discovered

https://neurosciencenews.com/multiple-s ... ora-10003/

Summary: A new study reports T cells are activated in the intestines and migrate to the brain, causing an inflammatory cascade that may lead to multiple sclerosis. Researchers say the gut microbiome may play a more significant role in the development and progression of MS than previously believed.

"In the journal Science Translational Medicine, the scientists report that T cells – i.e. the immune cells responsible for pathological processes – react to a protein called GDP-L-fucose synthase. This enzyme is formed in human cells as well as in bacteria frequently found in the gastrointestinal flora of patients suffering from multiple sclerosis. “We believe that the immune cells are activated in the intestine and then migrate to the brain, where they cause an inflammatory cascade when they come across the human variant of their target antigen,” says Mireia Sospedra"

More reactions here:

http://www.sci-news.com/medicine/gut-mi ... 06500.html

They say that in some patients called DRB3*02:02, an enzyme called GDP-l-fucose synthase has been shown to react with some CSF autoantibodies present in MS.

“T cells, i.e. the immune cells responsible for pathological processes, react to a protein called GDP-L-fucose synthase,” said lead author Dr. Mireia Sospedra of the University Hospital Zurich and colleagues.

“This enzyme is formed in human cells as well as in bacteria frequently found in the gastrointestinal flora of patients suffering from multiple sclerosis.”

“We believe that the immune cells are activated in the intestine and then migrate to the brain, where they cause an inflammatory cascade when they come across the human variant of their target antigen.”

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jimmylegs
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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by jimmylegs » Thu Oct 18, 2018 4:16 am

http://www.thisisms.com/forum/natural-a ... ml#p253767
excerpt:
"Recent findings have demonstrated the interplay between dietary components, gut microbiome, and autoantibody production. “Western” dietary patterns, such as high fat and high salt diets, can induce alterations in the gut microbiome that in turn affects IgA responses and the production of autoantibodies. This could contribute to multiple pathologies including autoimmune and inflammatory diseases."
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!

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frodo
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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by frodo » Thu Oct 18, 2018 4:53 am

jimmylegs wrote: "Recent findings have demonstrated the interplay between dietary components, gut microbiome, and autoantibody production. “Western” dietary patterns, such as high fat and high salt diets, can induce alterations in the gut microbiome that in turn affects IgA responses and the production of autoantibodies. This could contribute to multiple pathologies including autoimmune and inflammatory diseases."
Yes. The interaction was known before, but now they do not speak about generical IgA responses and abstract autoantibodies. From the original paper:

[...] we have identified guanosine diphosphate (GDP)–l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients

There is a page in wikipedia about that GDP, though it does not say too much.

https://en.wikipedia.org/wiki/GDP-L-fucose_synthase

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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by ElliotB » Thu Oct 18, 2018 6:21 am

This theory makes a lot of sense. It is surprising how little interest there is in the gut and gut health considering that most of the body's immune system (about 70% or more) resides there.

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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by jimmylegs » Thu Oct 18, 2018 9:00 am

brenda is a good spot to read up on enzymes

https://www.brenda-enzymes.org/enzyme.p ... =1.1.1.271
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!

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frodo
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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by frodo » Thu Oct 18, 2018 9:28 am

jimmylegs wrote:brenda is a good spot to read up on enzymes

https://www.brenda-enzymes.org/enzyme.p ... =1.1.1.271
Thanks, but I think this subject is well over my level.

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jimmylegs
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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by jimmylegs » Thu Oct 18, 2018 12:06 pm

you're welcome
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!

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frodo
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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by frodo » Fri Oct 19, 2018 11:32 am

More about the same subject.

In the article they speak about HLA DRB3 positive patients. It seems that the autoantigen found only appears in a group of patients that they call DRB3 positive. So I made a little research about it.

HLA seems to mean Human Leukocyte Antigen. It is a kind of grouping for people in such a way that they are compatible for transplants. This is why sometimes they speak about HLA-histocompatibility. The HLA-DRB3 group is the one that shows this kind of multiple sclerosis.

It seems that there is a wiki project called wikigenes, and the big news is that somebody had already found the relationship. It is reported there that HLA-DRB3 * 0202 was seen in all children with multiple sclerosis

https://www.wikigenes.org/e/gene/e/3125.html

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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by Leonard » Fri Oct 19, 2018 11:26 pm

jimmylegs wrote:http://www.thisisms.com/forum/natural-a ... ml#p253767
excerpt:
"Recent findings have demonstrated the interplay between dietary components, gut microbiome, and autoantibody production. “Western” dietary patterns, such as high fat and high salt diets, can induce alterations in the gut microbiome that in turn affects IgA responses and the production of autoantibodies. This could contribute to multiple pathologies including autoimmune and inflammatory diseases."

IgA production is also inhibited by EBV that "works" on the Peyer's Patches. Over 10's of millions of years of evolution, the virus has learned how to maximise its chances. This points to a viral dimension of autoimmunity and multiple pathologies. This also underlies the concept on http://www.thisisms.com/forum/general-d ... ml#p251748

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frodo
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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by frodo » Sat Oct 20, 2018 12:36 pm

IgA production is also inhibited by EBV that "works" on the Peyer's Patches. Over 10's of millions of years of evolution, the virus has learned how to maximise its chances. This points to a viral dimension of autoimmunity and multiple pathologies. This also underlies the concept on http://www.thisisms.com/forum/general-d ... ml#p251748
Interesting. It seems that everything begins to fit.

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frodo
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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by frodo » Tue Oct 23, 2018 1:57 am

The paper is not freely available but there is a review here

https://davidusharauli.blogspot.com/201 ... l.html?m=1

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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by Petr75 » Tue Oct 23, 2018 11:25 am

.. If guanosine diphosphate-L-fucose synthase turns out to be one of the elusive MS self-antigens, dosing patients with it might tame symptoms such as numbness and muscle weakness in much the same way that allergy shots prevent people from reacting to substances like ragweed pollen, Sospedra says. She and her colleagues plan to start to test this strategy with MS patients next year. https://www.sciencemag.org/news/2018/10 ... been-found

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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by Petr75 » Tue Oct 23, 2018 7:21 pm

An even more interesting part:

..The researchers wanted to determine which protein shards stimulated the patients’ T cells, so they tested 200 fragment mixtures, each containing 300 billion varieties. The two fragments with the strongest effect turned out to be part of a human enzyme called guanosine diphosphate-L-fucose synthase, which helps cells remodel sugars that are involved in everything from laying down memories to determining our blood type

https://www.sciencemag.org/news/2018/10 ... been-found

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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by Petr75 » Fri Oct 26, 2018 9:45 pm

2017 Jul 18
Glucocorticoid-associated blood glucose response and MS relapse recovery
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515601/

..Our data provide important insights into 1 possible mechanism that impaired glucose tolerance may be contributing to increased progression among patients with MS, even those without a confirmed diagnosis of diabetes.



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Re: Link Between Gut Flora and Multiple Sclerosis Discovered

Post by Petr75 » Mon Oct 29, 2018 12:45 pm

2018 Oct
Institute of Biochemistry, University Medicine Berlin, Germany
Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis.
https://www.ncbi.nlm.nih.gov/pubmed/30292675
PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197715/

Abstract
BACKGROUND:
Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for inflammatory, hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids have been implicated in the pathogenesis of multiple sclerosis since they augment vascular permeability and induce leukocyte migration into the brain. We explored the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro- (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with relapsing-remitting multiple sclerosis.
METHODS:
60 adults were prospectively recruited for this six months randomized controlled trial and the impact of dietary treatment on the Multiple Sclerosis Quality of Life-54 index (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored 24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we combined the two diet groups to a single pooled treatment group.
FINDINGS:
Inter-group comparison indicated that expression of the pro-inflammatory ALOX5 in the pooled treatment group was significantly (p < 0.05) reduced when compared with the control group. Moreover, intra-group comparison (same individuals before and after dietary treatment) suggested significantly impaired expression of other pro-inflammatory enzymes, such as COX1 (p < 0.001) and COX2 (p < 0.05). Finally, pretreatment cross-group analysis revealed a significant positive correlation between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation of ALOX5 and COX1 expression with the MSQoL-54 index.
INTERPRETATION:
Ketogenic diets can reduce the expression of enzymes involved in the biosynthesis of pro-inflammatory eicosanoids. Pharmacological interference with eicosanoid biosynthesis might constitute a strategy supplementing current therapeutic approaches for MS.

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