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 » Tue Jan 07, 2020 1:39 am

2014 Mar-Apr
Laboratory of Cellular and Molecular Immunology; National Institute of Allergy and Infectious Diseases, NIH; Bethesda
Role of SFB in autoimmune arthritis: an example of regulation of autoreactive T cell sensitivity in the gut.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063855/

Abstract

A key role for segmented filamentous bacteria (SFB) has recently been demonstrated in several mouse models of autoimmune diseases, including autoimmune arthritis and multiple sclerosis. The mechanism governing the activation of systemic autoreactive T cell responses by such commensals in the gut, however, remained elusive. In this addendum, we discuss recent results addressing the local regulation of autoreactive T cell sensitivity by these unique bacteria. We found that the presence of SFB in the gut microbiota was sufficient to promote a local inflammatory microenvironment altering the T cell-intrinsic desensitization process normally occurring in response to chronic self-antigen stimulation. In the absence of this key tolerance checkpoint, sustained chronic T cell proliferation, IFNγ production, and B cell activation eventually led to the development of enhanced pathologies in a Th1-driven T cell-transfer model of autoimmune arthritis.


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Re: Focus on the gut-brain axis

Post by Petr75 » Tue Jan 21, 2020 8:25 am

2020 Jan 17
State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
The progress of gut microbiome research related to brain disorders
https://www.ncbi.nlm.nih.gov/pubmed/31952509

Abstract

There is increasing evidence showing that the dynamic changes in the gut microbiota can alter brain physiology and behavior. Cognition was originally thought to be regulated only by the central nervous system. However, it is now becoming clear that many non-nervous system factors, including the gut-resident bacteria of the gastrointestinal tract, regulate and influence cognitive dysfunction as well as the process of neurodegeneration and cerebrovascular diseases. Extrinsic and intrinsic factors including dietary habits can regulate the composition of the microbiota. Microbes release metabolites and microbiota-derived molecules to further trigger host-derived cytokines and inflammation in the central nervous system, which contribute greatly to the pathogenesis of host brain disorders such as pain, depression, anxiety, autism, Alzheimer's diseases, Parkinson's disease, and stroke. Change of blood-brain barrier permeability, brain vascular physiology, and brain structure are among the most critical causes of the development of downstream neurological dysfunction. In this review, we will discuss the following parts: Overview of technical approaches used in gut microbiome studiesMicrobiota and immunityGut microbiota and metabolitesMicrobiota-induced blood-brain barrier dysfunctionNeuropsychiatric diseases ■ Stress and depression■ Pain and migraine■ Autism spectrum disordersNeurodegenerative diseases ■ Parkinson's disease■ Alzheimer's disease■ Amyotrophic lateral sclerosis■ Multiple sclerosisCerebrovascular disease ■ Atherosclerosis■ Stroke■ Arteriovenous malformationConclusions and perspectives.

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Petr75
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Re: Focus on the gut-brain axis

Post by Petr75 » Wed Feb 12, 2020 12:22 pm

2020 Jan 21
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland
Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity
https://pubmed.ncbi.nlm.nih.gov/3203864 ... oimmunity/

Abstract

There is increasing recognition of the role the microbiome plays in states of health and disease. Microbiome studies in systemic autoimmune diseases demonstrate unique microbial patterns in Inflammatory Bowel Disease, Rheumatoid Arthritis, and Systemic Lupus Erythematosus to a lesser extent, whereas there is no single bug or pattern that characterizes Multiple Sclerosis. Autoimmune diseases tend to share a predisposition for vitamin D deficiency, which alters the microbiome and integrity of the gut epithelial barrier. In this review, we summarize the influence of intestinal bacteria on the immune system, explore the microbial patterns that have emerged from studies on autoimmune diseases, and discuss how vitamin D deficiency may contribute to autoimmunity via its effects on the intestinal barrier function, microbiome composition, and/or direct effects on immune responses.



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Petr75
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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Feb 24, 2020 8:46 am

2020 Feb 14
Neuroscience Initiative, Advanced Science Research Center, The Graduate Center at the City University of New York
Gut-brain Communication in Demyelinating Disorders
https://pubmed.ncbi.nlm.nih.gov/3206607 ... disorders/


Abstract

Multiple Sclerosis (MS) is an autoimmune demyelinating disorder resulting from the interplay of genetic predisposition and environmental variables, including gut microbiota, diet and life style factors. Here, we first discuss the evidence supporting the effect of early life events, diet and body mass index on the composition of the microbiota, and then review studies on gut dysbiosis conducted in MS patients and in animal models. We address the effect of disease, immunomodulatory therapies, diet and probiotics on enrichment or depletion of gut microbial species. Finally, we discuss the ability of gut bacteria to produce toxins and metabolites which serve as signals for the cross-talk between the gut and the brain.

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Re: Focus on the gut-brain axis

Post by Petr75 » Tue Mar 10, 2020 12:15 pm

2020 Mar 6
Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany
Perturbation of Gut Microbiota Decreases Susceptibility but Does Not Modulate Ongoing Autoimmune Neurological Disease
https://pubmed.ncbi.nlm.nih.gov/3214371 ... l-disease/

Abstract

The gut microbiota regulates the host immune and nervous systems and plays an important role in the pathogenesis of autoimmune neurological disease multiple sclerosis (MS). There are considerable efforts currently being undertaken to develop therapies for MS based on the modulation of microbiota. Evidence from experimental models suggests that the manipulation of microbiota through diet or antibiotics prior to the disease development limits disease susceptibility. However, it is currently unclear if microbiota manipulation therapies would also have an impact on ongoing neurological disease. Here, we examined the effect of antibiotic-based microbiota modulation in spontaneous experimental autoimmune encephalomyelitis (EAE) mouse models of MS before and after the onset of autoimmune disease. Prophylactic antibiotic treatment led to a significant reduction of susceptibility to spontaneous EAE. In contrast, antibiotic treatment after the onset of spontaneous EAE did not show a significant amelioration. These results reveal that the perturbation of gut bacteria alters disease susceptibility but has minimal impact on the ongoing neurological disease.

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Re: Focus on the gut-brain axis

Post by Petr75 » Thu Mar 19, 2020 10:01 am

2020 Mar 12
Department of Neurology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium
Gut Microbiome Variation Is Associated to Multiple Sclerosis Phenotypic Subtypes
https://pubmed.ncbi.nlm.nih.gov/32162850/


Abstract

Objective: Multiple sclerosis (MS) is a heterogenous, inflammatory disease of the central nervous system. Microbiota alterations in MS versus healthy controls (HC) are observed, but results are inconsistent. We studied diversity, enterotypes, and specific gut microbial taxa variation between MS and HC, and between MS subgroups.

Methods: Amplicon sequencing of the 16S ribosomal RNA V4 region (Illumina MiSeq) was used to evaluate alpha and beta diversity, enterotypes, and relative taxa abundances on stool samples. MS subgroups were based on phenotype, disease course modifiers, and treatment status. Results were controlled for recently identified confounders of microbiota composition.

Results: Ninety-eight MS patients and 120 HC were included. Microbial richness was lower in interferon-treated (RRMS_I, N = 24) and untreated relapsing-remitting MS during relapse (RRMS_R, N = 4) when compared to benign (BMS, N = 20; Z = -3.07, Pcorr = 0.032 and Z = -2.68, Pcorr = 0.055) and primary progressive MS (PPMS, N = 26; Z = -2.39, Pcorr = 0.062 and Z = -2.26, Pcorr = 0.071). HC (N = 120) and active untreated MS (RRMS_U, N = 24) showed intermediate microbial richness. Enterotypes were associated with clinical subgroups (N = 218, χ2 = 36.10, P = 0.002), with Bacteroides 2 enterotype being more prevalent in RRMS_I. Butyricicoccus abundance was lower in PPMS than in RRMS_U (Z = -3.00, Pcorr = 0.014) and BMS (Z = -2.56, Pcorr = 0.031), lower in RRMS_I than in BMS (Z = -2.50, Pcorr = 0.034) and RRMS_U (Z = -2.91, Pcorr = 0.013), and inversely correlated with self-reported physical symptoms (rho = -0.400, Pcorr = 0.001) and disease severity (rho = -0.223, P = 0.027).

Interpretation: These results emphasize the importance of phenotypic subcategorization in MS-microbiome research, possibly explaining previous result heterogeneity, while showing the potential for specific microbiome-based biomarkers for disease activity and severity.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Mar 21, 2020 10:04 am

2020 Mar 10
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Gut Dysbiosis and Multiple Sclerosis
https://pubmed.ncbi.nlm.nih.gov/32169440/

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) and T cell-mediated autoimmune processes are assumed to be involved in its pathogenesis. Recently, accumulating evidence has indicated that commensal bacteria interact with the host immune system and that the alteration of commensal bacteria composition, termed dysbiosis, is associated with various autoimmune diseases including CNS autoimmune diseases. In this review, we introduce recent findings regarding the association between gut microbiota and MS and related diseases and microbiota function in an animal model of MS.

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Re: Focus on the gut-brain axis

Post by Petr75 » Thu Apr 23, 2020 11:34 am

2020 Apr 2
Nature Reviews Neurology
Microbiome varies between multiple sclerosis subtypes.
https://www.nature.com/articles/s41582-020-0354-2

Variations in the composition of the microbiota are associated with different multiple sclerosis (MS) phenotypes, according to a new study published in Annals of Clinical and Translational Neurology. The findings demonstrate the importance of patient stratification in studies of the microbiota in MS and also identify potential therapeutic targets for some patients.

Accumulating evidence suggests that alterations in the microbiota are important in MS, but the results of studies to date have varied. However, in most of these previous studies, patients with relapsing–remitting MS (RRMS) that had been exposed to various MS treatments were compared with healthy controls. In the new study, led by Marie D’hooghe and Jeroen Raes, the microbiome profiles of patients with different MS phenotypes were compared.

“By making subgroups based on clinical phenotype and disease course, this research project allowed us to investigate gut microbiome signals that could be related to clinical disease characteristics in MS,” says D’hooghe.

The study included 98 patients with MS and 120 healthy controls, 98 of whom were participants in the existing Flemish Gut Flora Project. Patients with MS were divided into five subgroups on the basis of their clinical phenotypes: untreated RRMS, untreated RRMS during a relapse, untreated benign MS, interferon-treated RRMS and non-active primary progressive MS.

Stool samples from the patients and controls were analysed to determine the composition of their microbiota. “We used 16S amplicon sequencing, a technique in which a specific region of the 16S ribosomal RNA gene is amplified and sequenced,” explains Jeroen Raes. “Using this, we are able to build microbiota composition profiles.”

No measures of microbiota composition differed significantly between all patients with MS and healthy controls. However, measures of microbial richness and the abundance of several microbial taxa did differ between MS phenotypes.

Patients were also classified into one of four enterotypes — groups defined by specific clusters of bacterial species that make up the microbiota. An enterotype known as Bacteroides2 (Bact2) was enriched among patients with interferon-treated RRMS and untreated RRMS during a relapse...

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Re: Focus on the gut-brain axis

Post by Petr75 » Tue Jun 02, 2020 10:39 am

2020 May 3
Department of Biotechnology, Dalian Medical University, Dalian, China
Rapamycin and MCC950 Modified Gut Microbiota in Experimental Autoimmune Encephalomyelitis Mouse by Brain Gut Axis
https://pubmed.ncbi.nlm.nih.gov/32376270/

Abstract

Aims: Multiple sclerosis (MS) whose pathogenesis is still unclear is a chronic progressive disease in the central nervous system. Gut microbiota can directly or indirectly affect the immune system through the brain gut axis to engage in the occurrence and development of the disease.

Materials and methods: C57BL/6 mice which were immunized by MOG35-55 to prepare experimental autoimmune encephalomyelitis (EAE) animal models were treated with rapamycin and MCC950 (CP-456773) in combination or separately. After sequencing the 16S rRNA V4 region of gut microbiota, the species, abundance and composition of gut microbiota were analyzed by Alpha diversity, Bata diversity and LEfSe analysis. The pathological changes and the expression of CD4 and CD8 of brain, large intestine and spleen were detected.

Key findings: The results showed that rapamycin and MCC950 could alleviate the progression of the disease by inducing autophagy and inhibiting the immune response. The Alpha diversity of EAE model group was no significant difference compering to control group while the number of OTUs was decreased. After the treatment by rapamycin and MCC950, the abundance and composition of gut microbiota was relatively recovered, which was close to that of normal mice.

Significance: Inhibiting immune cell-mediated inflammation and restoring the composition of gut microbiota may help to alleviate the clinical symptoms of multiple sclerosis. Furthermore, to research the regulatory effect between immune response and gut microbiota may be a new strategy for the prevention and treatment of multiple sclerosis.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Jul 19, 2020 11:15 am

2020 Jun
Ventura Clinical Trials, Malibu
Rapid improvement in Alzheimer's disease symptoms following fecal microbiota transplantation: a case report
https://pubmed.ncbi.nlm.nih.gov/32600151/

Abstract

Alzheimer's disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson's disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome-gut-brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Aug 22, 2020 11:02 pm

2020 Jul 7
IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis
https://pubmed.ncbi.nlm.nih.gov/32733460/

Abstract

Background: Butyric acid (BA) is a short-chain fatty acid (SCFA) with anti-inflammatory properties, which promotes intestinal barrier function. Medium-chain fatty acids (MCFA), including caproic acid (CA), promote TH1 and TH17 differentiation, thus supporting inflammation. Aim: Since most SCFAs are absorbed in the cecum and colon, the measurement of BA in peripheral blood could provide information on the health status of the intestinal ecosystem. Additionally, given the different immunomodulatory properties of BA and CA the evaluation of their serum concentration, as well as their ratio could be as a simple and rapid biomarker of disease activity and/or treatment efficacy in MS. Methods: We evaluated serum BA and CA concentrations, immune parameters, intestinal barrier integrity and the gut microbiota composition in patients with multiple sclerosis (MS) comparing result to those obtained in healthy controls. Results: In MS, the concentration of BA was reduced and that of CA was increased. Concurrently, the microbiota was depleted of BA producers while it was enriched in mucin-degrading, pro-inflammatory components. The reduced serum concentration of BA seen in MS patients correlated with alterations of the barrier permeability, as evidenced by the higher plasma concentrations of lipopolysaccharide and intestinal fatty acid-binding protein, and inflammation. Specifically, CA was positively associated with CD4+/IFNγ+ T lymphocytes, and the BA/CA ratio correlated positively with CD4+/CD25high/Foxp3+ and negatively with CD4+/IFNγ+ T lymphocytes. Conclusion: The gut microbiota dysbiosis found in MS is possibly associated with alterations of the SCFA/MCFA ratio and of the intestinal barrier; this could explain the chronic inflammation that characterizes this disease. SCFA and MCFA quantification could be a simple biomarker to evaluate the efficacy of therapeutic and rehabilitation procedures in MS.

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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Aug 24, 2020 9:58 am

2019 Dec 20
Department of Neurology, Yale University School of Medicine, New Haven
CXCR3+ T cells in multiple sclerosis correlate with reduced diversity of the gut microbiome
https://pubmed.ncbi.nlm.nih.gov/32743517/

Abstract

Multiple sclerosis (MS) is a genetically mediated autoimmune disease characterized by inflammation in the central nervous system (CNS). Disease onset is thought to occur when autoreactive T cells orchestrate a cascade of events in the CNS resulting in white and grey matter inflammation and axonal degeneration. It is unclear what triggers the activation of CNS-reactive T cells and their polarization into inflammatory subsets. Mounting evidence from animal and human studies supports the hypothesis that the gut microbiome affects MS pathogenesis. We investigated the association between the gut microbiome and inflammatory T cell subsets in relapsing-remitting MS patients and healthy controls. Gut microbiome composition was characterized by sequencing the V4 region of the 16S rRNA gene from fecal DNA, and inflammatory T cell subsets were characterized by flow cytometry. We identified an altered gut microbiome in MS patients, including decreased abundance of Coprococcus, Clostridium, and an unidentified Ruminococcaceae genus. Among circulating immune cells, patients had increased expression of CXCR3 in both CD4 and CD8 T cells, and both CD4+CXCR3+ and CD8+CXCR3+ populations expressing the gut-homing α4β7 integrin receptor were increased. Finally, we show that alpha diversity inversely correlated with a CXCR3+ Th1 phenotype in MS. These findings indicate the presence of an aberrant gut-immune axis in patients with MS.

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