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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Petr75
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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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Petr75
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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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Petr75
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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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Petr75
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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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Petr75
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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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