Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential

Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the comm...

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Main Authors: Mohammad Hosein Nemati, Esmaeil Yazdanpanah, Roya Kazemi, Niloufar Orooji, Sepehr Dadfar, Valentyn Oksenych, Dariush Haghmorad
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/4/435
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author Mohammad Hosein Nemati
Esmaeil Yazdanpanah
Roya Kazemi
Niloufar Orooji
Sepehr Dadfar
Valentyn Oksenych
Dariush Haghmorad
author_facet Mohammad Hosein Nemati
Esmaeil Yazdanpanah
Roya Kazemi
Niloufar Orooji
Sepehr Dadfar
Valentyn Oksenych
Dariush Haghmorad
author_sort Mohammad Hosein Nemati
collection DOAJ
description Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut–brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., <i>Prevotella</i> and <i>Faecalibacterium</i>) were suggested to lay protective roles, whereas <i>Akkermansia muciniphila</i> was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut–brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.
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spelling doaj-art-5899c1ecf12d468286a10fbd96f50abd2025-08-20T02:24:44ZengMDPI AGBiology2079-77372025-04-0114443510.3390/biology14040435Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker PotentialMohammad Hosein Nemati0Esmaeil Yazdanpanah1Roya Kazemi2Niloufar Orooji3Sepehr Dadfar4Valentyn Oksenych5Dariush Haghmorad6Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, IranImmunology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, IranStudent Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, IranStudent Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, IranStudent Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, IranBroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, NorwayDepartment of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, IranMultiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut–brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., <i>Prevotella</i> and <i>Faecalibacterium</i>) were suggested to lay protective roles, whereas <i>Akkermansia muciniphila</i> was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut–brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.https://www.mdpi.com/2079-7737/14/4/435gut microbiotamultiple sclerosisimmune modulationdysbiosistherapeutic interventions
spellingShingle Mohammad Hosein Nemati
Esmaeil Yazdanpanah
Roya Kazemi
Niloufar Orooji
Sepehr Dadfar
Valentyn Oksenych
Dariush Haghmorad
Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential
Biology
gut microbiota
multiple sclerosis
immune modulation
dysbiosis
therapeutic interventions
title Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential
title_full Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential
title_fullStr Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential
title_full_unstemmed Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential
title_short Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential
title_sort microbiota driven mechanisms in multiple sclerosis pathogenesis therapeutic strategies and biomarker potential
topic gut microbiota
multiple sclerosis
immune modulation
dysbiosis
therapeutic interventions
url https://www.mdpi.com/2079-7737/14/4/435
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