Focus on the gut-brain axis

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Petr75
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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Jul 01, 2019 9:05 am

2019 Apr 26
Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
MAdCAM-1-Mediated Intestinal Lymphocyte Homing Is Critical for the Development of Active Experimental Autoimmune Encephalomyelitis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503766/

Abstract
Lymphocyte homing into the intestine is mediated by binding of leukocytes to mucosal addressin cell adhesion molecule 1 (MAdCAM-1), expressed on endothelial cells. Currently, the immune system of the gut is considered a major modulator not only of inflammatory bowel disease, but also of extra-intestinal autoimmune disorders, including multiple sclerosis (MS). Despite intense research in this field, the exact role of the intestine in the pathogenesis of (neuro-)inflammatory disease conditions remains to be clarified. This prompted us to investigate the role of MAdCAM-1 in immunological processes in the intestine during T cell-mediated autoimmunity of the central nervous system (CNS). Using the experimental autoimmune encephalomyelitis model of MS, we show that MAdCAM-1-deficient (MAdCAM-1-KO) mice are less susceptible to actively MOG35-55-induced disease. Protection from disease was accompanied by decreased numbers of immune cells in the lamina propria and Peyer's patches as well as reduced immune cell infiltration into the spinal cord. MOG35-55-recall responses were intact in other secondary lymphoid organs of MAdCAM-1-KO mice. The composition of specific bacterial groups within the microbiome did not differ between MAdCAM-1-KO mice and controls, while MAdCAM-1-deficiency severely impaired migration of MOG35-55-activated lymphocytes to the gut. Our data indicate a critical role of MAdCAM-1 in the development of CNS inflammation by regulating lymphocyte homing to the intestine, and may suggest a role for the intestinal tract in educating lymphocytes to become encephalitogenic.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Jul 07, 2019 2:08 am

2019 May 21
Department of Neurology, San Raffaele Hospital, Milan, Italy
Caesarean section and infant formula feeding are associated with an earlier age of onset of multiple sclerosis.
https://www.ncbi.nlm.nih.gov/pubmed/31158806

Abstract
Mode of delivery and lactation are among the earliest factors influencing gut microbiota composition and potentially MS risk, but their contribution to MS susceptibility has been controversial. We investigated whether these factors could influence age at MS onset (AAO) on 2055 RRMS patients (mean age 28.4 years). Patients born by means of a caesarean section (10.9%) had an earlier AAO than those born through natural delivery (-5.2 years, p < 0.001). Patients fed with infant formula had an earlier AAO compared to patients breastfed, particularly considering those breastfed for at least 6 months (-4.2 years, p < 0.001). The association of vaginal delivery and natural breastfeeding with a later AAO of MS was particularly apparent in patients without a family history of MS, while disappeared in patients with familiarity for MS. The results suggest these modifiable environmental factors which act at the population level may have an influence on the onset of the disease.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Jul 20, 2019 11:56 am

2019 May 30
Baylor College of Medicine, Department of Pathology & Immunology, and Texas Children's Microbiome Center, Houston
Microbiota stratification identifies disease-specific alterations in neuro-Behçet's disease and multiple sclerosis.
https://www.ncbi.nlm.nih.gov/pubmed/31172918

Abstract
OBJECTIVES:
Altered gut microbiota community dynamics are implicated in diverse human diseases including inflammatory disorders such as neuro-Behçet's disease (NBD) and multiple sclerosis (MS). Traditionally, microbiota communities are analysed uniformly across control and disease groups, but recent reports of subsample clustering indicate a potential need for analytical stratification. The objectives of this study are to analyse and compare faecal microbiota community signatures of ethno-geographical, age and gender matched adult healthy controls (HC), MS and NBD individuals.
METHODS:
Faecal microbiota community compositions in adult HC (n=14), NBD patients (n=13) and MS (n=13) were analysed by 16S rRNA gene sequencing and standard bioinformatics pipelines. Bipartite networks were then used to identify and re-analyse dominant compositional clusters in respective groups.
RESULTS:
We identified Prevotella and Bacteroides dominated subsample clusters in HC, MS, and NBD cohorts. Our study confirmed previous reports that Prevotella is a major dysbiotic target in these diseases. We demonstrate that subsample stratification is required to identify significant disease-associated microbiota community shifts with increased Clostridiales evident in Prevotella-stratified NBD and Bacteroides-stratified MS patients.
CONCLUSIONS:
Patient cohort stratification may be needed to facilitate identification of common microbiota community shifts for causation testing in disease.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Jul 28, 2019 11:04 am

2019 Aug
Institute of Genetic and Biomedical Research (IRGB), Italian National Research Council (CNR), Cittadella Universitaria di Monserrato, Sardinia, Italy
The gut microbiota perspective for interventions in MS.
https://www.ncbi.nlm.nih.gov/pubmed/31176875

Abstract
The heritable genetic variation that explains phenotypic differences in a population fluctuates for different autoimmune disorders. Particularly in multiple sclerosis (MS) etiology, modest genetic and major environmental effects emerge. Increasingly recognized as a major environmentally shaped contributor to disease and treatment outcomes are gut microbiota. As discussed here, the observed impact of gut microbiome on MS pathophysiology, involves both quantitative and functional changes in composition, metabolism, gut permeability, homeostasis and modulation of the immune system. Although the first supplementary therapeutic interventions have been approached in general autoimmune disorders they are relatively cruder and a translation of knowledge from other pathologies is valuable but still required. Consequently initial therapeutic interventions with microbiota for autoimmune disorders could be correspondingly improved.

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Re: Focus on the gut-brain axis

Post by NHE » Sun Jul 28, 2019 4:42 pm

Petr75 wrote:
Sun Jul 28, 2019 11:04 am
2019 Aug
Institute of Genetic and Biomedical Research (IRGB), Italian National Research Council (CNR), Cittadella Universitaria di Monserrato, Sardinia, Italy
The gut microbiota perspective for interventions in MS.
https://www.ncbi.nlm.nih.gov/pubmed/31176875

Abstract
The heritable genetic variation that explains phenotypic differences in a population fluctuates for different autoimmune disorders. Particularly in multiple sclerosis (MS) etiology, modest genetic and major environmental effects emerge. Increasingly recognized as a major environmentally shaped contributor to disease and treatment outcomes are gut microbiota. As discussed here, the observed impact of gut microbiome on MS pathophysiology, involves both quantitative and functional changes in composition, metabolism, gut permeability, homeostasis and modulation of the immune system. Although the first supplementary therapeutic interventions have been approached in general autoimmune disorders they are relatively cruder and a translation of knowledge from other pathologies is valuable but still required. Consequently initial therapeutic interventions with microbiota for autoimmune disorders could be correspondingly improved.
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https://www.sciencedirect.com/science/a ... via%3Dihub

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Re: Focus on the gut-brain axis

Post by Petr75 » Wed Sep 04, 2019 11:24 am

2019 Oct
Department of Physiology and Pharmacology, School of Medicine, Alborz University of Medical Sciences, Alborz, Iran
Gut microbiota depletion from early adolescence alters adult immunological and neurobehavioral responses in a mouse model of multiple sclerosis
https://www.ncbi.nlm.nih.gov/pubmed/31247271

Abstract

Emerging evidence indicates that gut microbiota interacts with immune and nervous systems in the host and plays a critical role in the pathogenesis of multiple sclerosis (MS) and many psychiatric disorders such as depression and anxiety. The aim of this study was to explore the influence of gut bacterial depletion from early adolescence on adult immunological and neurobehavioral responses in mice with experimental-autoimmune-encephalomyelitis (EAE). We used an animal model of gut microbiota depletion induced by antibiotics from weaning to adulthood to assess clinical signs, cognitive function and depression-and anxiety-related symptoms in non-EAE and EAE-induced mice. We measured levels of interferon (IFN)-γ, interleukin (IL)-17A and IL-10 in serum, and BDNF, IL-1β and tumor necrosis factor (TNF)-α) in the hippocampus. Antibiotic-treated mice displayed a significant delay in the onset of clinical symptoms of EAE. However, a higher severity of EAE was found between days 19-22 post-immunization in antibiotics-treated mice, while a reduction in the clinical signs of MS was observed at days 24-25 post-immunization. Antibiotic administration decreased IFN-γ and IL-17A levels and increased IL-10 in serum of EAE-induced mice. Antibiotic treatment significantly decreased hippocampal BDNF and enhanced learning and memory impairments in EAE-induced mice. However, no significant changes were found in non-EAE mice. Non-EAE and EAE mice treated with antibiotics exhibited increased anxiety-related behaviors, whereas depression-related symptoms and increased hippocampal TNF-α and IL-1β were only observed in EAE-induced mice treated with antibiotics. This study supports the view that depletion of gut microbiota by antibiotics from weaning profoundly impacts adult immunological and neurobehavioral responses.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Sep 08, 2019 4:26 am

2019 Jun 14
Neuroimmunology Group, Functional and Systems Neurobiology Department, Instituto Cajal, CSIC, Madrid, Spain
Manipulation of Gut Microbiota Influences Immune Responses, Axon Preservation, and Motor Disability in a Model of Progressive Multiple Sclerosis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587398/

Abstract
Gut microbiota dysbiosis has been implicated in MS and other immune diseases, although it remains unclear how manipulating the gut microbiota may affect the disease course. Using a well-established model of progressive MS triggered by intracranial infection with Theiler's murine encephalomyelitis virus (TMEV), we sought to determine whether dysbiosis induced by oral antibiotics (ABX) administered on pre-symptomatic and symptomatic phases of the disease influences its course. We also addressed the effects of microbiota recolonization after ABX withdrawn in the presence or absence of probiotics. Central and peripheral immunity, plasma acetate and butyrate levels, axon damage and motor disability were evaluated. The cocktail of ABX prevented motor dysfunction and limited axon damage in mice, which had fewer CD4+ and CD8+ T cells in the CNS, while gut microbiota recolonization worsened motor function and axonal integrity. The underlying mechanisms of ABX protective effects seem to involve CD4+CD39+ T cells and CD5+CD1d+ B cells into the CNS. In addition, microglia adopted a round amoeboid morphology associated to an anti-inflammatory gene profile in the spinal cord of TMEV mice administered ABX. The immune changes in the spleen and mesenteric lymph nodes were modest, yet ABX treatment of mice limited IL-17 production ex vivo. Collectively, our results provide evidence of the functional relevance of gut microbiota manipulation on the neurodegenerative state and disease severity in a model of progressive MS and reinforce the role of gut microbiota as target for MS treatment.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Sep 22, 2019 2:38 am

2019 Jul 16
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City
The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634972/

Abstract

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.

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Re: Focus on the gut-brain axis

Post by Leonard » Mon Sep 23, 2019 12:06 am

Petr75 wrote:
Sun Sep 22, 2019 2:38 am
2019 Jul 16
Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City
The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634972/

Abstract

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.
Thanks Petr for this article. The link did not work but I found the full article here: https://elifesciences.org/articles/47117

Although the article does not mention specifically the herpes virus, it does make reference to this study that links MS to herpes. https://www.ncbi.nlm.nih.gov/pubmed/22583435

The article may be interesting for the neurologists because it connects the current work on the microbiome with many of the facets they are known with from within their own domain. But at the same time, the article fully confirms the bigger picture that emerges here: viewtopic.php?f=1&t=15188&start=885#p258372

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Re: Focus on the gut-brain axis

Post by NHE » Mon Sep 23, 2019 12:38 am

Leonard wrote:
Mon Sep 23, 2019 12:06 am
Thanks Petr for this article. The link did not work but I found the full article here: https://elifesciences.org/articles/47117
The link has been fixed.

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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Sep 23, 2019 7:11 am

Thank (NHE and Leo)

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Re: Focus on the gut-brain axis

Post by Petr75 » Thu Sep 26, 2019 3:42 am

2019 Jul 18
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada/Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary
Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity
https://www.ncbi.nlm.nih.gov/pubmed/31317818

Abstract
BACKGROUND:
Recent evidence suggests a role for the gut-brain axis in the pathophysiology of multiple sclerosis (MS).
MATERIALS AND METHODS:
We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured.
RESULTS:
Zonulin concentrations were significantly higher when a concurrent magnetic resonance imaging (MRI) confirmed the presence of blood-brain barrier (BBB) disruption (Gad+ RRMS) and were correlated with tight junction proteins. IBABP and D-lactate were elevated in people with RRMS compared to controls, but did not discriminate between Gad+ and Gad- subgroups. Baseline zonulin concentrations were associated with 1-year disease progression in progressive MS.
CONCLUSIONS:
People with MS have altered biomarkers of intestinal barrier integrity. Zonulin concentrations are associated with 1-year disease progression in progressive MS and closely mirror BBB breakdown in RRMS. Zonulin may mediate breakdown of both the intestinal barrier and the BBB in gut dysbiosis through the regulation of tight junctions. This could explain how the gut-brain axis modulates neuroinflammation in MS.

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Re: Focus on the gut-brain axis

Post by Petr75 » Fri Sep 27, 2019 11:45 am

2019
PC Microbiome Ireland, University College Cork, Cork, Ireland
Monocyte mobilisation, microbiota & mental illness.
https://www.ncbi.nlm.nih.gov/pubmed/31330299

Abstract
The gastrointestinal microbiome has emerged as a key player in regulating brain and behaviour. This has led to the strategy of targeting the gut microbiota to ameliorate disorders of the central nervous system. Understanding the underlying signalling pathways in which the microbiota impacts these disorders is crucial for the development of future therapeutics for improving CNS functionality. One of the major pathways through which the microbiota influences the brain is the immune system, where there is an increasing appreciation for the role of monocyte trafficking in regulating brain homeostasis. In this review, we will shed light on the role of monocyte trafficking as a relay of microbiota signals in conditions where the central nervous system is in disorder, such as stress, peripheral inflammation, ageing, traumatic brain injury, stroke, multiple sclerosis, Alzheimer's disease and Parkinson's disease. We also cover how the gastrointestinal microbiota is implicated in these mental illnesses. In addition, we aim to discuss how the monocyte system can be modulated by the gut microbiota to mitigate disorders of the central nervous system, which will lead to novel microbiota-targeted strategies.

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Re: Focus on the gut-brain axis

Post by Petr75 » Fri Oct 25, 2019 2:56 am

2019 Jul 19
Department of Surgical Sciences, University of Turin, Turin, Italy
Inflammation in gastrointestinal disorders: prevalent socioeconomic factors
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650093/

Abstract
Western populations harbor a chronic inflammation pattern that lacks organ cardinal signs (edema, increased temperature, pain, and impaired function), releases increased levels of C-reactive protein, and often runs a creeping clinical course with generalized debilitating disease superimposed on system-specific involvement, mostly including nervous tissue (multiple sclerosis, Parkinson's syndromes), joints (arthritis), and skin (psoriasis). A finalistic interpretation may apply to the consideration of the gut as the source of inflammation. In fact, these kind of local events as well as the remote manifestations named above, could be conditioned by the microbiome, the huge cell population indwelling the gut which is under growing scrutiny. The role of the gut as a barrier organ justifies lingering submucosal inflammation as a patrolling activity to maintain bodily integrity; the microbiome, launching inflammogenic signals in response to abrupt diet changes, confers to gut inflammation a socioeconomic vector calling for hitherto unrecognized multi-disciplinary interventions.

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Re: Focus on the gut-brain axis

Post by Leonard » Fri Oct 25, 2019 6:06 am

Petr75 wrote:
Fri Oct 25, 2019 2:56 am
2019 Jul 19
Department of Surgical Sciences, University of Turin, Turin, Italy
Inflammation in gastrointestinal disorders: prevalent socioeconomic factors
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650093/

Abstract
Western populations harbor a chronic inflammation pattern that lacks organ cardinal signs (edema, increased temperature, pain, and impaired function), releases increased levels of C-reactive protein, and often runs a creeping clinical course with generalized debilitating disease superimposed on system-specific involvement, mostly including nervous tissue (multiple sclerosis, Parkinson's syndromes), joints (arthritis), and skin (psoriasis). A finalistic interpretation may apply to the consideration of the gut as the source of inflammation. In fact, these kind of local events as well as the remote manifestations named above, could be conditioned by the microbiome, the huge cell population indwelling the gut which is under growing scrutiny. The role of the gut as a barrier organ justifies lingering submucosal inflammation as a patrolling activity to maintain bodily integrity; the microbiome, launching inflammogenic signals in response to abrupt diet changes, confers to gut inflammation a socioeconomic vector calling for hitherto unrecognized multi-disciplinary interventions.
The full story is here: viewtopic.php?f=1&t=15188&start=885#p258372

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