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 » Sat Oct 24, 2020 12:02 pm

2020 Sep 8
Division of Gastroenterology, Department of Internal Medicine, Rush University Medical Center, Chicago
Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis
https://www.frontiersin.org/articles/10 ... 00978/full

..Longitudinal Assessment of Gait Metrics

During the gait condition, the subject's normal gait metrics were primarily enhanced after each FMT, and significantly improved over time indicating improved walking and balance (Figures 3A–F, Supplementary Table 11). Stride time significantly decreased over time (Bonferroni: P < 0.0001) indicating subject's walking speed improved. Stride distance significantly increased over time (Bonferroni: P < 0.0001) suggesting subject's walking steps increased in distance. Step width did not change significantly from baseline to Week 52 (Bonferroni: P > 0.9999). Cadence significantly increased over time (Bonferroni: P < 0.0001) indicating subject's number of steps/minute increased. Average pelvis forward velocity significantly increased over time (Bonferroni: P < 0.0001), approximating the increased speed of the body center of mass. Pelvis smoothness significantly increased over time (Bonferroni: P < 0.0001), suggesting the subject's body walking motion was more fluid. Side gaze gait, alternating gaze gait, and within lab visit results in Supplementary Figures 10–12, Supplementary Tables 12–14..

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Petr75
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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Oct 25, 2020 8:50 am

2020 Oct 6
Department of Pathology, University of Utah School of Medicine, Salt Lake City
Molecular patterns from a human gut-derived Lactobacillus strain suppress pathogenic infiltration of leukocytes into the central nervous system
https://pubmed.ncbi.nlm.nih.gov/33023618/

Abstract

Background: Multiple sclerosis (MS) is an inflammatory demyelinating disease that affects 2.5 million people worldwide. Growing evidence suggests that perturbation of the gut microbiota, the dense collection of microorganisms that colonize the gastrointestinal tract, plays a functional role in MS. Indeed, specific gut-resident bacteria are altered in patients with MS compared to healthy individuals, and colonization of gnotobiotic mice with MS-associated microbiota exacerbates preclinical models of MS. However, defining the molecular mechanisms by which gut commensals can remotely affect the neuroinflammatory process remains a critical gap in the field.

Methods: We utilized monophasic experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice and relapse-remitting EAE in SJL/J mice to test the effects of the products from a human gut-derived commensal strain of Lactobacillus paracasei (Lb).

Results: We report that Lb can ameliorate preclinical murine models of MS with both prophylactic and therapeutic administrations. Lb ameliorates disease through a Toll-like receptor 2-dependent mechanism via its microbe-associated molecular patterns that can be detected in the systemic circulation, are sufficient to downregulate chemokine production, and can reduce immune cell infiltration into the central nervous system (CNS). In addition, alterations in the gut microbiota mediated by Lb-associated molecular patterns are sufficient to provide partial protection against neuroinflammatory diseases.

Conclusions: Local Lb modulation of the gut microbiota and the shedding of Lb-associated molecular patterns into the circulation may be important physiological signals to prevent aberrant peripheral immune cell infiltration into the CNS and have relevance to the development of new therapeutic strategies for MS.

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Re: Focus on the gut-brain axis

Post by Petr75 » Fri Oct 30, 2020 5:55 am

2020 Oct 12
University Sarajevo School of Science and Technology, Bosnia and Herzegovina
Using data science for medical decision making case: role of gut microbiome in multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/33046051/

Abstract

Background: A decade ago, the advancements in the microbiome data sequencing techniques initiated the development of research of the microbiome and its relationship with the host organism. The development of sophisticated bioinformatics and data science tools for the analysis of large amounts of data followed. Since then, the analyzed gut microbiome data, where microbiome is defined as a network of microorganisms inhabiting the human intestinal system, has been associated with several conditions such as irritable bowel syndrome - IBS, colorectal cancer, diabetes, obesity, and metabolic syndrome, and lately in the study of Parkinson's and Alzheimer's diseases as well. This paper aims to provide an understanding of differences between microbial data of individuals who have been diagnosed with multiple sclerosis and those who were not by exploiting data science techniques on publicly available data.

Methods: This study examines the relationship between multiple sclerosis (MS), an autoimmune central nervous system disease, and gut microbial community composition, using the samples acquired by 16s rRNA sequencing technique. We have used three different sets of MS samples sequenced during three independent studies (Jangi et al, Nat Commun 7:1-11, 2016), (Miyake et al, PLoS ONE 10:0137429, 2015), (McDonald et al, Msystems 3:00031-18, 2018) and this approach strengthens our results. Analyzed sequences were from healthy control and MS groups of sequences. The extracted set of statistically significant bacteria from the (Jangi et al, Nat Commun 7:1-11, 2016) dataset samples and their statistically significant predictive functions were used to develop a Random Forest classifier. In total, 8 models based on two criteria: bacteria abundance (at six taxonomic levels) and predictive functions (at two levels), were constructed and evaluated. These include using taxa abundances at different taxonomy levels as well as predictive function analysis at different hierarchical levels of KEGG pathways.

Results: The highest accuracy of the classification model was obtained at the genus level of taxonomy (76.82%) and the third hierarchical level of KEGG pathways (70.95%). The second dataset's 18 MS samples (Miyake et al, PLoS ONE 10:0137429, 2015) and 18 self-reported healthy samples from the (McDonald et al, Msystems 3:00031-18, 2018) dataset were used to validate the developed classification model. The significance of this step is to show that the model is not overtrained for a specific dataset but can also be used on other independent datasets. Again, the highest classification model accuracy for both validating datasets combined was obtained at the genus level of taxonomy (70.98%) and third hierarchical level of KEGG pathways (67.24%). The accuracy of the independent set remained very relevant.

Conclusions: Our results demonstrate that the developed classification model provides a good tool that can be used to suggest the presence or absence of MS condition by collecting and analyzing gut microbiome samples. The accuracy of the model can be further increased by using sequencing methods that allow higher taxa resolution (i.e. shotgun metagenomic sequencing).

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Re: Focus on the gut-brain axis

Post by Petr75 » Sat Oct 31, 2020 12:35 am

2020 Oct 19
Department of Biomedical and Health Sciences, University of Vermont, Burlington,
Medical Systems Biology Group, Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany
Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity
https://pubmed.ncbi.nlm.nih.gov/33077601/

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. The etiology of MS is multifactorial, with disease risk determined by genetics and environmental factors. An emerging risk factor for immune-mediated diseases is an imbalance in the gut microbiome. However, the identity of gut microbes associated with disease risk, their mechanisms of action, and the interactions with host genetics remain obscure. To address these questions, we utilized the principal autoimmune model of MS, experimental autoimmune encephalomyelitis (EAE), together with a genetically diverse mouse model representing 29 unique host genotypes, interrogated by microbiome sequencing and targeted microbiome manipulation. We identified specific gut bacteria and their metabolic functions associated with EAE susceptibility, implicating short-chain fatty acid metabolism as a key element conserved across multiple host genotypes. In parallel, we used a reductionist approach focused on two of the most disparate phenotypes identified in our screen. Manipulation of the gut microbiome by transplantation and cohousing demonstrated that transfer of these microbiomes into genetically identical hosts was sufficient to modulate EAE susceptibility and systemic metabolite profiles. Parallel bioinformatic approaches identified Lactobacillus reuteri as a commensal species unexpectedly associated with exacerbation of EAE in a genetically susceptible host, which was functionally confirmed by bacterial isolation and commensal colonization studies. These results reveal complex interactions between host genetics and gut microbiota modulating susceptibility to CNS autoimmunity, providing insights into microbiome-directed strategies aimed at lowering the risk for autoimmune disease and underscoring the need to consider host genetics and baseline gut microbiome composition.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Dec 06, 2020 12:16 pm

2020 Nov
Department of Microbiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran; Student Research Committee, Guilan University of Medical Sciences, Rasht, Iran
Gut microbiome and multiple sclerosis: New insights and perspective
https://pubmed.ncbi.nlm.nih.gov/33182024/

Abstract

The human gastrointestinal microbiota, also known as the gut microbiota living in the human gastrointestinal tract, has been shown to have a significant impact on several human disorders including rheumatoid arthritis, diabetes, obesity, and multiple sclerosis (MS). MS is an inflammatory disease characterized by the destruction of the spinal cord and nerve cells in the brain due to an attack of immune cells, causing a wide range of harmful symptoms related to inflammation in the central nervous system (CNS). Despite extensive studies on MS that have shown that many external and genetic factors are involved in its pathogenesis, the exact role of external factors in the pathophysiology of MS is still unclear. Recent studies on MS and experimental autoimmune encephalomyelitis (EAE), an animal model of encephalitis, have shown that intestinal microbiota may play a key role in the pathogenesis of MS. Therefore, modification of the intestinal microbiome could be a promising strategy for the future treatment of MS. In this study, the characteristics of intestinal microbiota, the relationship between intestine and brain despite the blood-brain barrier, various factors involved in intestinal microbiota modification, changes in intestinal microbial composition in MS, intestinal microbiome modification strategies, and possible use of intestinal microbiome and factors affecting it have been discussed.

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Re: Focus on the gut-brain axis

Post by Petr75 » Sun Dec 13, 2020 4:06 am

2020 Nov 20
Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco
Gut microbiota-specific IgA + B cells traffic to the CNS in active multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/33219152/


Abstract

Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota-specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.

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Leonard
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Re: Focus on the gut-brain axis

Post by Leonard » Mon Dec 14, 2020 6:32 am

the true value of this last study lies in the fact that it was done with a very wide group of people from all over the world.

I think the interaction between brains and the rest of the body including the gut is regulated via the idiotypic regulatory network and the immune homunculus.

see for instance figure 1 in viewtopic.php?f=1&t=15188&start=915#p260601

these people should start to think bigger in overall holistic concepts (such as figure 1) and help me with my thesis.

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Petr75
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Re: Focus on the gut-brain axis

Post by Petr75 » Tue Dec 15, 2020 4:07 am

2020 Nov 16
Grupo de Investigación de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) / Red Española de Esclerosis Múltiple (REEM), Madrid, Spain
Acetate correlates with disability and immune response in multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/33240608/

Abstract

Background: Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis.

Objectives: To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations.

Methods: Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment.

Results: Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e-4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e-4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r = - 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001).

Conclusions: Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

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Re: Focus on the gut-brain axis

Post by Petr75 » Fri Feb 05, 2021 1:50 am

2021 Jan 16
Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, China
Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain
https://pubmed.ncbi.nlm.nih.gov/33510784/


Abstract

Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).



full: https://www.hindawi.com/journals/grp/2021/6699268/

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Petr75
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Re: Focus on the gut-brain axis

Post by Petr75 » Mon Feb 22, 2021 11:37 pm

2021 Feb 5
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
IL-17 controls central nervous system autoimmunity through the intestinal microbiome
https://pubmed.ncbi.nlm.nih.gov/33547052/


Abstract

Interleukin-17A- (IL-17A) and IL-17F-producing CD4+ T helper cells (TH17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). TH17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, TH17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which correlated with an altered composition of their gut microbiota. However, loss of IL-17A/F in TH cells did not diminish their encephalitogenic capacity. Reconstitution of a wild-type-like intestinal microbiota or reintroduction of IL-17A specifically into the gut epithelium of IL-17A/F-deficient mice reestablished their susceptibility to EAE. Thus, our data demonstrated that IL-17A and IL-17F are not encephalitogenic mediators but rather modulators of intestinal homeostasis that indirectly alter CNS-directed autoimmunity.

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