Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis |
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Authors: | Laura Calvo-Barreiro Herena Eixarch Xavier Montalban Carmen Espejo |
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Affiliation: | Servei de Neurologia-Neuroimmunologia, Centre d''Esclerosi Múltiple de Catalunya, Vall d''Hebron Institut de Recerca, Hospital Universitari Vall d''Hebron, 08035 Barcelona, Spain;Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain |
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Abstract: | The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients. |
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Keywords: | AHR aryl hydrocarbon receptor BBB blood-brain barrier CNS central nervous system CIS clinically isolated syndrome EDSS expanded disability status scale EAE experimental autoimmune encephalomyelitis DC dendritic cell DMF dimethyl fumarate DMT disease-modifying treatment GF germ-free GA glatiramer acetate HCs healthy controls I3S indoxyl-3-sulfate IFN interferon IL interleukin iMSMS international multiple sclerosis microbiome study IELs intraepithelial lymphocytes ?/? LCFAs long-chain fatty acids LNs lymph nodes MRI magnetic resonance imagining MCFAs medium-chain fatty acids MS multiple sclerosis MOG myelin oligodendrocyte glycoprotein PBMCs peripheral blood mononuclear cells PSA polysaccharide A RIS radiologically isolated syndrome reg regulatory T RR relapsing-remitting SCFAs short-chain fatty acids SPF specific pathogen-free Th T helper TJ tight junction TLR toll-like receptor TGF transforming growth factor Trp tryptophan TNF tumour necrosis factor WT wild-type Microbiota Dysbiosis Probiotic Immune regulation Experimental autoimmune encephalomyelitis Multiple sclerosis |
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