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 » Fri Oct 25, 2019 7:05 am

Thank you Leo.

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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Oct 28, 2019 9:43 am

2019 Aug 28
Chemical and Systems Biology Department, Stanford University School of Medicine, Stanford
Latent-period stool proteomic assay of multiple sclerosis model indicates protective capacity of host-expressed protease inhibitors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713765/

Abstract
Diseases are often diagnosed once overt symptoms arise, ignoring the prior latent period when effective prevention may be possible. Experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, exhibits such disease latency, but the molecular processes underlying this asymptomatic period remain poorly characterized. Gut microbes also influence EAE severity, yet their impact on the latent period remains unknown. Here, we show the latent period between immunization and EAE's overt symptom onset is characterized by distinct host responses as measured by stool proteomics. In particular, we found a transient increase in protease inhibitors that inversely correlated with disease severity. Vancomycin administration attenuated both EAE symptoms and protease inhibitor induction potentially by decreasing immune system reactivity, supporting a subset of the microbiota's role in modulating the host's latent period response. These results strengthen previous evidence of proteases and their inhibitors in EAE and highlight the utility stool-omics for revealing complex, dynamic biology.

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Re: Focus on the gut-brain axis

Post by Petr75 » Tue Oct 29, 2019 10:38 am

2019 Aug 16
Experimental Diabetes Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
How the Interplay Between the Commensal Microbiota, Gut Barrier Integrity, and Mucosal Immunity Regulates Brain Autoimmunity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706873/

Abstract
The intestinal barrier provides the host with a strong defense line against the external environment playing also a pivotal role in the crosstalk between the gut microbiota and the immune system. Notably, increasing lines of evidence concerning autoimmune disorders such as Multiple Sclerosis (MS) report an imbalance in both intestinal microbiota composition and mucosal immunity activation, along with an alteration of gut barrier permeability, suggesting this complex network plays a crucial role in modulating the course of autoimmune responses occurring in tissues outside the gut such as the central nervous system (CNS). Here, we review current knowledge on how gut inflammation and breakage of gut barrier integrity modulates the interplay between the commensal gut microbiota and the immune system and its role in shaping brain immunity.



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Leonard
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Re: Focus on the gut-brain axis

Post by Leonard » Wed Oct 30, 2019 6:53 am

I think they still miss essential elements, that is the virus and SNPs.

But yes, the gut biota influence the immune system/immunity, both inside the brain (microglia as the first line of defense against viral infection) and outside the brain.
And with that the anti-viral properties. https://elifesciences.org/articles/47117
And of course the epigenetics of the cells.

The full story is here: viewtopic.php?f=1&t=15188&start=885#p258372

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Nov 10, 2019 6:17 am

2019 Aug 28
Department of Neurosciences, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Centre for Experimental Neurological Therapies, Sapienza University, Rome, Italy
The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724505/

Abstract
The gut barrier consists of several components, including the mucus layer, made of mucins and anti-bacterial molecule, the epithelial cells, connected by tight junction proteins, and a mixed population of cells involved in the interplay with microbes, such as M cells, elongations of "antigen presenting cells" dwelling the lamina propria, intraepithelial lymphocytes and Paneth cells secreting anti-bacterial peptides. Recently, the influence of intestinal permeability (IP) changes on organs far from gut has been investigated, and IP changes in multiple sclerosis (MS) have been described. A related topic is the microbiota dysfunction that underpins the development of neuroinflammation in animal models and human diseases, including MS. It becomes now of interest to better understand the mechanisms through which IP changes contribute to pathophysiology of neuroinflammation. The following aspects seem of relevance: studies on other biomarkers of IP alterations; the relationship with known risk factors for MS development, such as vitamin D deficiency; the link between blood brain barrier and gut barrier breakdown; the effects of IP increase on microbial translocation and microglial activation; the parallel patterns of IP and neuroimmune changes in MS and neuropsychiatric disorders, that afflict a sizable proportion of patients with MS. We will also discuss the therapeutic implications of IP changes, considering the impact of MS-modifying therapies on gut barrier, as well as potential approaches to enhance or protect IP homeostasis.


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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Nov 16, 2019 1:59 am

2019 Oct 8
Laboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland
Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis
https://www.ncbi.nlm.nih.gov/pubmed/31597098

Abstract
Multiple sclerosis (MS) is a common autoimmune disease of the CNS. Although an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we show that encephalitogenic Th17 cells infiltrate the colonic lamina propria before neurological symptom development in two murine MS models, active and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 cell intestinal homing by blocking the α4β7-integrin and its ligand MAdCAM-1 pathway impairs T cell migration to the large intestine and dampens EAE severity in the Th17 cell adoptive transfer model. Mechanistically, myelin-specific Th17 cells proliferate in the colon and affect gut microbiota composition. The beneficial effect of blocking the α4β7-integrin and its ligand MAdCAM-1 pathway on EAE is interdependent with gut microbiota. Those results show that disrupting myelin-specific Th17 cell trafficking to the large intestine harnesses neuroinflammation and suggests that the gut environment and microbiota catalyze the encephalitogenic properties of Th17 cells.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Nov 23, 2019 12:32 am

2019 Nov 5
CRC Scotland & London
Departments of Neurology & Immunology, Mayo Clinic College of Medicine & Science, Rochester, USA
Multiple Sclerosis: Melatonin, Orexin, and Ceramide Interact with Platelet Activation Coagulation Factors and Gut-Microbiome-Derived Butyrate in the Circadian Dysregulation of Mitochondria in Glia and Immune Cells.
https://www.ncbi.nlm.nih.gov/pubmed/31694154

Abstract
Recent data highlight the important roles of the gut microbiome, gut permeability, and alterations in mitochondria functioning in the pathophysiology of multiple sclerosis (MS). This article reviews such data, indicating two important aspects of alterations in the gut in the modulation of mitochondria: (1) Gut permeability increases toll-like receptor (TLR) activators, viz circulating lipopolysaccharide (LPS), and exosomal high-mobility group box (HMGB)1. LPS and HMGB1 increase inducible nitric oxide synthase and superoxide, leading to peroxynitrite-driven acidic sphingomyelinase and ceramide. Ceramide is a major driver of MS pathophysiology via its impacts on glia mitochondria functioning; (2) Gut dysbiosis lowers production of the short-chain fatty acid, butyrate. Butyrate is a significant positive regulator of mitochondrial function, as well as suppressing the levels and effects of ceramide. Ceramide acts to suppress the circadian optimizers of mitochondria functioning, viz daytime orexin and night-time melatonin. Orexin, melatonin, and butyrate increase mitochondria oxidative phosphorylation partly via the disinhibition of the pyruvate dehydrogenase complex, leading to an increase in acetyl-coenzyme A (CoA). Acetyl-CoA is a necessary co-substrate for activation of the mitochondria melatonergic pathway, allowing melatonin to optimize mitochondrial function. Data would indicate that gut-driven alterations in ceramide and mitochondrial function, particularly in glia and immune cells, underpin MS pathophysiology. Aryl hydrocarbon receptor (AhR) activators, such as stress-induced kynurenine and air pollutants, may interact with the mitochondrial melatonergic pathway via AhR-induced cytochrome P450 (CYP)1b1, which backward converts melatonin to N-acetylserotonin (NAS). The loss of mitochnodria melatonin coupled with increased NAS has implications for altered mitochondrial function in many cell types that are relevant to MS pathophysiology. NAS is increased in secondary progressive MS, indicating a role for changes in the mitochondria melatonergic pathway in the progression of MS symptomatology. This provides a framework for the integration of diverse bodies of data on MS pathophysiology, with a number of readily applicable treatment interventions, including the utilization of sodium butyrate.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Nov 23, 2019 7:05 am

2019 Nov 8
Department of Neurology, New York University School of Medicine, New York
Gut microbiome of treatment-naïve MS patients of different ethnicities early in disease course.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841666/

Abstract

Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium, compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Nov 23, 2019 10:06 am

2019 Oct 24
Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada
Skin Exposure to Narrow Band Ultraviolet (UVB) Light Modulates the Human Intestinal Microbiome.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821880/

Abstract
The recent worldwide rise in idiopathic immune and inflammatory diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBD) has been linked to Western society-based changes in lifestyle and environment. These include decreased exposure to sunlight/UVB light and subsequent impairment in the production of vitamin D, as well as dysbiotic changes in the makeup of the gut microbiome. Despite their association, it is unclear if there are any direct links between UVB light and the gut microbiome. In this study we investigated whether exposing the skin to Narrow Band Ultraviolet B (NB-UVB) light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota. The effects of NB-UVB light were studied in a clinical pilot study using a healthy human female cohort (n = 21). Participants were divided into those that took vitamin D supplements throughout the winter prior to the start of the study (VDS+) and those who did not (VDS-). After three NB-UVB light exposures within the same week, the serum 25(OH)D levels of participants increased on average 7.3 nmol/L. The serum response was negatively correlated to the starting 25-hydroxy vitamin D [25(OH)D] serum concentration. Fecal microbiota composition analysis using 16S rRNA sequencing showed that exposure to NB-UVB significantly increased alpha and beta diversity in the VDS- group whereas there were no changes in the VDS+ group. Bacteria from several families were enriched in the VDS- group after the UVB exposures according to a Linear Discriminant Analysis (LDA) prediction, including Lachnospiracheae, Rikenellaceae, Desulfobacteraceae, Clostridiales vadinBB60 group, Clostridia Family XIII, Coriobacteriaceae, Marinifilaceae, and Ruminococcus. The serum 25(OH)D concentrations showed a correlation with the relative abundance of the Lachnospiraceae, specifically members of the Lachnopsira and Fusicatenibacter genera. This is the first study to show that humans with low 25(OH)D serum levels display overt changes in their intestinal microbiome in response to NB-UVB skin exposure and increases in 25(OH)D levels, suggesting the existence of a novel skin-gut axis that could be used to promote intestinal homeostasis and health. Clinical Trial Registration: clinicaltrials.gov, NCT03962673. Registered 23 May 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT ... 673&rank=1.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Nov 30, 2019 1:45 am

2019 Nov 18
Wellcome-MRC Stem Cell Institute, University of Cambridgege, United Kingdom
The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination.
https://www.pnas.org/content/early/2019 ... 1905787116

Abstract
The microbiota is now recognized as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress toward therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination-the regeneration of myelin sheaths-also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics impair oligodendrocyte progenitor cell responses during remyelination and further our understanding of how mammalian regeneration relates to the microbiota.

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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Dec 02, 2019 10:39 pm

2019 Nov 18
APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Ireland
The gut microbiome in neurological disorders.
https://www.ncbi.nlm.nih.gov/pubmed/31753762

Abstract
Research into the role of the gut microbiome in modulating brain function has rapidly increased over the past 10 years, albeit chiefly in animal models. Increasing clinical and preclinical evidence implicates the microbiome as a possible key susceptibility factor for neurological disorders, including Alzheimer's disease, autism spectrum disorder, multiple sclerosis, Parkinson's disease, and stroke. Cross-sectional clinical studies are bolstering the concept of altered microbial composition contributing to the pathophysiology of such diseases. However, the field is nascent, and interpretation of such data is often difficult given that the composition of the microbiome is influenced by various factors such as diet and exercise. Longitudinal studies and randomised controlled trials in humans are needed to find out if targeting the microbiome can yield novel therapeutic strategies. Systems biology approaches will also be important in integrating such data with genomic and metabolomic datasets from clinical cohorts with neurological disease to help guide individual treatment selection.

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Re: Focus on the gut-brain axis

Post by Petr75 » Wed Dec 04, 2019 10:38 am

2019 Nov 6
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China
The Role of the Gut Microbiota in the Pathogenesis of Parkinson's Disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851172/

Abstract

It is well-recognized that the gut microbiota (GM) is crucial for gut function, metabolism, and energy cycles. The GM also has effects on neurological outcomes via many mechanisms, such as metabolite production and the gut-brain axis. Emerging evidence has gradually indicated that GM dysbiosis plays a role in several neurological diseases, such as Parkinson's disease (PD), Alzheimer's disease, depression, and multiple sclerosis. Several studies have observed that PD patients generally suffer from gastrointestinal disorders and GM dysbiosis prior to displaying motor symptoms, but the specific link between the GM and PD is not clearly understood. In this review, we aim to summarize what is known regarding the correlation between the GM and PD pathologies, including direct, and indirect evidence.


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Re: Focus on the gut-brain axis

Post by Petr75 » Fri Dec 06, 2019 9:48 am

2019 Dec 2
APC Microbiome Ireland, University College Cork, Cork, Ireland
You've Got Male: Sex and the Microbiota-Gut Brain Axis Across the Lifespan.
https://www.ncbi.nlm.nih.gov/pubmed/31805290


Abstract

Sex is a critical factor in the diagnosis and development of a number of mental health disorders including autism, schizophrenia, depression, anxiety, Parkinson's disease, multiple sclerosis, anorexia nervosa and others; likely due to differences in sex steroid hormones and genetics. Recent evidence suggests that sex can also influence the complexity and diversity of microbes that we harbour in our gut; and reciprocally that our gut microbes can directly and indirectly influence sex steroid hormones and central gene activation. There is a growing emphasis on the role of gastrointestinal microbiota in the maintenance of mental health and their role in the pathogenesis of disease. In this review, we introduce mechanisms by which gastrointestinal microbiota are thought to mediate positive health benefits along the gut-brain axis, we report how they may be modulated by sex, the role they play in sex steroid hormone regulation, and their sex-specific effects in various disorders relating to mental health.

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