Focus on the gut-brain axis

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Petr75
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Re: Focus on the gut-brain axis

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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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Re: Focus on the gut-brain axis

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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

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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

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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

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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

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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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Re: Focus on the gut-brain axis

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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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Re: Focus on the gut-brain axis

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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

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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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Re: Focus on the gut-brain axis

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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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Re: Focus on the gut-brain axis

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2021 Mar 24
Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Odisha, India
Unravelling the potential of gut microbiota in sustaining brain health and their current prospective towards development of neurotherapeutics
https://pubmed.ncbi.nlm.nih.gov/33763767/

Abstract

Increasing incidences of neurological disorders, such as Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are being reported, but an insight into their pathology remains elusive. Findings have suggested that gut microbiota play a major role in regulating brain functions through the gut-brain axis. A unique bidirectional communication between gut microbiota and maintenance of brain health could play a pivotal role in regulating incidences of neurodegenerative diseases. Contrarily, the present life style with changing food habits and disturbed circadian rhythm may contribute to gut homeostatic imbalance and dysbiosis leading to progression of several neurological disorders. Therefore, dysbiosis, as a primary factor behind intestinal disorders, may also augment inflammation, intestinal and blood-brain barrier permeability through microbiota-gut-brain axis. This review primarily focuses on the gut-brain axis functions, specific gut microbial population, metabolites produced by gut microbiota, their role in regulating various metabolic processes and role of gut microbiota towards development of neurodegenerative diseases. However, several studies have reported a decrease in abundance of a specific gut microbial population and a corresponding increase in other microbial family, with few findings revealing some contradictions. Reports also showed that colonization of gut microbiota isolated from patients suffering from neurodegenerative disease leads to the development of enhance pathological outcomes in animal models. Hence, a systematic understanding of the dominant role of specific gut microbiome towards development of different neurodegenerative diseases could possibly provide novel insight into the use of probiotics and microbial transplantation as a substitute approach for treating/preventing such health maladies.
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Re: Focus on the gut-brain axis

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2021 May 11
From the Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), France
Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis
https://pubmed.ncbi.nlm.nih.gov/33975914/


Abstract

Objective: Based on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS.

Methods: We investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing.

Results: We show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (r = -0.647, p < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, p < 0.001).

Conclusions: Gut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.
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Re: Focus on the gut-brain axis

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2021 May
ReMedy International Research Agenda Programme, Centre of New Technologies, University of Warsaw, Poland
Endocrine cross-talk between the gut microbiome and glial cells in development and disease
https://pubmed.ncbi.nlm.nih.gov/34019340/

Abstract

Glial cells make up the major cellular component of the nervous system. Glial development is usually investigated through perturbations of host genetics, although non-host-derived signalling molecules can also regulate glial cells. Indeed, gut microbiome colonisation and the presence of microbiome-derived factors in the blood coincide with glial cell development. Emerging data suggest that the gut microbiome can regulate gliogenesis, myelination and glial epigenetics. Neurodegenerative diseases are characterised by changes in the gut microbiome and glial dysfunction. This perspective discusses the ways in which microbiome-derived molecules can engage in cross-talk with glial cells during development and in dysfunctional glial diseases.
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Re: Focus on the gut-brain axis

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2021 May 5
Department of Immunology, Harvard Medical School, Boston, MA, United States
Exploring the Gut-Brain Axis for the Control of CNS Inflammatory Demyelination: Immunomodulation by Bacteroides fragilis' Polysaccharide A
https://pubmed.ncbi.nlm.nih.gov/34025663/

Abstract

The symbiotic relationship between animals and their resident microorganisms has profound effects on host immunity. The human microbiota comprises bacteria that reside in the gastrointestinal tract and are involved in a range of inflammatory and autoimmune diseases. The gut microbiota's immunomodulatory effects extend to extraintestinal tissues, including the central nervous system (CNS). Specific symbiotic antigens responsible for inducing immunoregulation have been isolated from different bacterial species. Polysaccharide A (PSA) of Bacteroides fragilis is an archetypical molecule for host-microbiota interactions. Studies have shown that PSA has beneficial effects in experimental disease models, including experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis (MS). Furthermore, in vitro stimulation with PSA promotes an immunomodulatory phenotype in human T cells isolated from healthy and MS donors. In this review, we discuss the current understanding of the interactions between gut microbiota and the host in the context of CNS inflammatory demyelination, the immunomodulatory roles of gut symbionts. More specifically, we also discuss the immunomodulatory effects of B. fragilis PSA in the gut-brain axis and its therapeutic potential in MS. Elucidation of the molecular mechanisms responsible for the microbiota's impact on host physiology offers tremendous promise for discovering new therapies.

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Re: Focus on the gut-brain axis

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2021 Jul 1
1. Department of Neurology, School of Medicine, Washington University in St. Louis, Missouri, USA.
2. University of Milan, Italy
Targeting the gut to treat multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/34196310/


Abstract
The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies and cohorts vary greatly. Small clinical and preclinical trials in pwMS and mouse models, in which microbial composition was manipulated through the use of antibiotics, fecal microbiota transplantation, and probiotic supplements, have provided promising outcomes in preventing CNS inflammation. However, results are not always consistent, and large-scale randomized controlled trials are lacking. Herein, we give an overview of how the GBA could contribute to MS pathogenesis, examine the different approaches tested to modulate the GBA, and discuss how they may impact neuroinflammation and demyelination in the CNS.
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