Focus on the gut-brain axis

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Petr75
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Focus on the gut-brain axis

Post by Petr75 » Sun Nov 04, 2018 12:14 pm

2018 Oct 7
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Canada
Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome.
https://www.ncbi.nlm.nih.gov/pubmed/30310254

Abstract
The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.

Free PMC Article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175760/

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Re: Focus on the gut-brain axis

Post by NHE » Sun Nov 04, 2018 3:36 pm

This paper states...
One of the first components of the intestinal barrier is a thick mucus layer forming a protective film, enriched by secretory IgA and antimicrobial peptides and proteins. Oral supplementation with lecithin and phosphatidylcholine can adhere to the intestinal mucosa, strengthening the mucus layer and improving barrier function[44-46].
Another paper states that 2 g/day of phosphatidylcholine was helpful for restoring the gut's mucosal layer and relieving symptoms of chronic steroid-refractory ulcerative colitis. Sunflower lecithin containing phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine is available fairly inexpensively. Has anybody tried this?

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Re: Focus on the gut-brain axis

Post by Leonard » Tue Nov 06, 2018 3:18 am

A bad gut leads to a deficient methylation/failure of epigenetic regulation and cellular expression.
This in turn leads to elevated peroxynitrite and mounting oxidative stress at cellular level.
See also steps 5 and 6 of: http://www.thisisms.com/forum/general-d ... ml#p251748
It is yet another pubication that fits the overall concept.

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Re: Focus on the gut-brain axis

Post by frodo » Wed Nov 07, 2018 6:37 am

Thanks. A lot of papers are comming out now speaking about the gut connection. Let's hope that they are now on the right track.

By the way, the paper is freely available here:

https://www.wjgnet.com/1007-9327/full/v24/i37/4217.htm

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Re: Focus on the gut-brain axis

Post by Petr75 » Wed Nov 07, 2018 7:49 am

The primary problem is gut, I also hope.

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Re: Focus on the gut-brain axis

Post by ArthurJ » Wed Nov 21, 2018 3:08 am

NHE wrote:Another paper states that 2 g/day of phosphatidylcholine was helpful for restoring the gut's mucosal layer and relieving symptoms of chronic steroid-refractory ulcerative colitis. Sunflower lecithin containing phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine is available fairly inexpensively. Has anybody tried this?
I've decided to try the sunflower lecithin. I take 2 tablespoons per day. I mix it with some plain yogurt. The lecithin gives it a smooth texture. This provides roughly 5 g phosphatidylcholine, 3.6 g phosphatidylinositol and 2.2 g phosphatidylethanolamine per day. I've only been taking it for a couple of days, but I seem to feel better afterwards. Will update as time progresses.

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Re: Focus on the gut-brain axis

Post by Petr75 » Fri Nov 23, 2018 9:22 am

2018 Oct 19
Department of Immunology and Rheumatology, Mayo Clinic, Rochester, MN, USA
Role of the intestinal microbiome in autoimmune diseases and its use in treatments.
https://www.ncbi.nlm.nih.gov/pubmed/30366573

Abstract
The role of the intestinal microbiome in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes is being increasingly appreciated.
Many studies have reported that the compositions of the intestinal microbiomes of patients with these autoimmune diseases are different from those of healthy individuals. Analyses of the intestinal microbiome of humans suggest that various factors affect the composition of the intestinal microbiome, including, but not limited to: geographical location, diet, sex, and age. However, patients with rheumatoid arthritis and type 1 diabetes show unique intestinal microbiome profile even after considering these confounding factors. This review will describe the known differences in the microbial composition for each of the aforementioned autoimmune diseases, how it impacts the immune system, and how these compositions may potentially be modulated by treatments with probiotics, prebiotics, and other microbiome altering therapies.

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Re: Focus on the gut-brain axis

Post by ArthurJ » Wed Dec 12, 2018 8:50 am

ArthurJ wrote:I've decided to try the sunflower lecithin. I take 2 tablespoons per day. I mix it with some plain yogurt. The lecithin gives it a smooth texture. This provides roughly 5 g phosphatidylcholine, 3.6 g phosphatidylinositol and 2.2 g phosphatidylethanolamine per day. I've only been taking it for a couple of days, but I seem to feel better afterwards. Will update as time progresses.
I've since reduced my dosage to 1 tablespoon per day. I still feel better after consuming it so I plan to continue for now.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Dec 16, 2018 3:45 am

2018 Nov 6
UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California
Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria
PMC Article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222044/

Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria, which primarily belong to the classes Bacilli and Clostridia in the phylum Firmicutes, have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa (primarily in the class Clostridia) and show that their presence correlates with impaired differentiation of IL-10-secreting, regulatory T lymphocytes in vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of proinflammatory, IFN-γ+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control-derived spore-forming bacteria were able to induce similar IL-10-expressing Treg immunoregulatory responses, thus ameliorating symptoms of experimental allergic encephalomyelitis (EAE). Our analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth. IMPORTANCE To address the impact of microbiome on disease development, it is essential to go beyond a descriptive study and evaluate the physiological importance of microbiome changes. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of spore-forming microbial communities, revealing novel functional correlations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform-resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is correlated with impaired immunomodulatory responses in vitro.

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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Dec 17, 2018 11:22 pm

2018 Nov 10
Servicio de Neurología. Hospital San Pedro, Logroño, La Rioja, España
Disease of the holobiont, the example of multiple sclerosis
https://www.ncbi.nlm.nih.gov/pubmed/30424933

Abstract
In recent years there has been a revolution regarding the role of the microbiota in different diseases, most of them within the spectrum of inflammatory and autoimmune diseases, associated with the development of metagenomics and the concept of holobiont, a large organism together with its microbiota. Specifically, in Multiple Sclerosis, multiple evidence points to the role of the microbiota in experimental autoimmune encephalomyelitis, animal model of the disease, and several articles have been published in recent years about differences in intestinal microbiota among patients with multiple sclerosis and control subjects. We review in this article the concept of holobiont and the gut microbiota functions, as well as the evidence accumulated about the role of the microbiota in experimental autoimmune encephalomyelitis and multiple sclerosis. Nowadays, there is a lot of evidence showing the role of the microbiota in the genesis, prevention and treatment of experimental autoimmune encephalomyelitis based mainly on three immunological pillars, the Th1-Th17 / Th2 balance, the Treg cells and the humoral immunity. It is also well documented that there are differences in the microbiota of patients with MS that are associated with a different expression of genes related to inflammation.

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Re: Focus on the gut-brain axis

Post by Petr75 » Tue Dec 18, 2018 12:21 am

2018 Nov 13
Haney MM, Ericsson AC, Lever TE.
Effects of Intraoperative Vagal Nerve Stimulation on the Gastrointestinal Microbiome in a Mouse Model of Amyotrophic Lateral Sclerosis.
https://www.ncbi.nlm.nih.gov/pubmed/30424824

Abstract
The gastrointestinal microbiota (GM) plays a fundamental role in health and disease and contributes to the bidirectional signaling between the gastrointestinal system and brain. The direct line of communication between these organ systems is through the vagus nerve. Therefore, vagal nerve stimulation (VNS), a commonly used technique for multiple disorders, has potential to modulate the enteric microbiota, enabling investigation and possibly treatment of numerous neurologic disorders in which the microbiota has been linked with disease. Here we investigate the effect of VNS in a mouse model of amyotrophic lateral sclerosis (ALS). B6SJL-Tg(SOD1*G93A)dl1Gur (SOD1dl) and wildtype mice underwent ventral neck surgeryto access the vagus nerve. During surgery, the experimental group received 1 h of VNS, whereas the sham group underwent 1 h of sham treatment. The third (control) group did not undergo any surgical manipulation. Fecal samples were collected before surgery and at 8 d after the initial collection. Microbial DNA was sequenced to determine the GM profiles at both time points. GM profiles did not differ between genotypes at either the initial or end point. In addition, VNS did not alter GM populations, according to the parameters chosen in this study, indicating that this short intraoperative treatment is safeand has no lasting effects on the GM. Future studies are warranted to determine whether different stimulation parametersor chronic use of VNS affect GM profiles.

-------------------------------------------
Vagal Nerve and CCSVI (MS) ??

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Re: Focus on the gut-brain axis

Post by Petr75 » Thu Dec 20, 2018 7:59 am

2018 Oct 30
CERVO Brain Research Center, Quebec City, QC, Canada
Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
Department of Cell Systems and Anatomy, The University of Texas Health Science Center, San Antonio, TX, United States.
PRASE, Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
Latitude, Vitamin D, Melatonin, and Gut Microbiota Act in Concert to Initiate Multiple Sclerosis: A New Mechanistic Pathway.
PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232868/

Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the etiology of MS is still largely unknown, scientists believe that the interaction of several endogenous and exogenous factors may be involved in this disease. Epidemiologists have seen an increased prevalence of MS in countries at high latitudes, where the sunlight is limited and where the populations have vitamin D deficiency and high melatonin levels. Although the functions and synthesis of vitamin D and melatonin are contrary to each other, both are involved in the immune system. While melatonin synthesis is affected by light, vitamin D deficiency may be involved in melatonin secretion. On the other hand, vitamin D deficiency reduces intestinal calcium absorption leading to gut stasis and subsequently increasing gut permeability. The latter allows gut microbiota to transfer more endotoxins such as lipopolysaccharides (LPS) into the blood. LPS stimulates the production of inflammatory cytokines within the CNS, especially the pineal gland. This review summarizes the current findings on the correlation between latitude, sunlight and vitamin D, and details their effects on intestinal calcium absorption, gut microbiota and neuroinflammatory mediators in MS. We also propose a new mechanistic pathway for the initiation of MS.

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Re: Focus on the gut-brain axis

Post by tzootsi » Thu Dec 20, 2018 2:26 pm

Very interesting. looks like vitamin D may protect against leaky gut - something that Aston Embry was talking about 10 years ago.

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Re: Focus on the gut-brain axis

Post by Petr75 » Fri Dec 21, 2018 10:00 am

2018 Dec
Lerner Research Institute, Cleveland Clinic, Cleveland, USA
IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases
https://www.ncbi.nlm.nih.gov/pubmed/30449598

Abstract
Breakdown of the blood-brain barrier (BBB) precedes lesion formation in the brains of multiple sclerosis (MS) patients. Since recent data implicate disruption of the small intestinal epithelial barrier (IEB) in the pathogenesis of MS, we hypothesized that the increased permeability of the BBB and IEB are mechanistically linked. Zonulin, a protein produced by small intestine epithelium, can rapidly increase small intestinal permeability. Zonulin blood levels are elevated in MS, but it is unknown whether zonulin can also disrupt the BBB. Increased production of IL-17A and IFN-γ has been implicated in the pathogenesis of MS, epilepsy, and stroke, and these cytokines impact BBB integrity after 24 h. We here report that primary human brain microvascular endothelial cells expressed the EGFR and PAR2 receptors necessary to respond to zonulin, and that zonulin increased BBB permeability to a 40 kDa dextran tracer within 1 h. Moreover, both IL-17A and IFN-γ also rapidly increased BBB and IEB permeability. By using confocal microscopy, we found that exposure of the IEB to zonulin, IFN-γ, or IL-17A in vitro rapidly modified the localization of the TJ proteins, ZO-1, claudin-5, and occludin. TJ disassembly was accompanied by marked depolymerization of the peri-junctional F-actin cytoskeleton. Our data indicate that IFN-γ, IL-17A, or zonulin can increase the permeability of the IEB and BBB rapidly in vitro, by modifying TJs and the underlying actin cytoskeleton. These observations may help clarify how the gut-brain axis mediates the pathogenesis of neuro-inflammatory diseases.

wiki https://en.wikipedia.org/wiki/Zonulin
Last edited by Petr75 on Mon Jan 28, 2019 1:37 pm, edited 2 times in total.

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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Jan 28, 2019 1:32 pm

2019 Jan 24
Department of Immunology, University of Toronto, Canada
Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco
Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10.
https://www.ncbi.nlm.nih.gov/pubmed/30612739

Abstract
Plasma cells (PC) are found in the CNS of multiple sclerosis (MS) patients, yet their source and role in MS remains unclear. We find that some PC in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) originate in the gut and produce immunoglobulin A (IgA). Moreover, we show that IgA+ PC are dramatically reduced in the gut during EAE, and likewise, a reduction in IgA-bound fecal bacteria is seen in MS patients during disease relapse. Removal of plasmablast (PB) plus PC resulted in exacerbated EAE that was normalized by the introduction of gut-derived IgA+ PC. Furthermore, mice with an over-abundance of IgA+ PB and/or PC were specifically resistant to the effector stage of EAE, and expression of interleukin (IL)-10 by PB plus PC was necessary and sufficient to confer resistance. Our data show that IgA+ PB and/or PC mobilized from the gut play an unexpected role in suppressing neuroinflammation.

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