{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:37:49Z","timestamp":1791689869843,"version":"4.3.4"},"reference-count":174,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>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\u2013brain 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., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila 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\u2013brain 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.<\/jats:p>","DOI":"10.3390\/biology14040435","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T06:53:46Z","timestamp":1744872826000},"page":"435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1011-3415","authenticated-orcid":false,"given":"Mohammad Hosein","family":"Nemati","sequence":"first","affiliation":[{"name":"Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran"},{"name":"Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmaeil","family":"Yazdanpanah","sequence":"additional","affiliation":[{"name":"Immunology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roya","family":"Kazemi","sequence":"additional","affiliation":[{"name":"Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran"},{"name":"Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloufar","family":"Orooji","sequence":"additional","affiliation":[{"name":"Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran"},{"name":"Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-6711","authenticated-orcid":false,"given":"Sepehr","family":"Dadfar","sequence":"additional","affiliation":[{"name":"Student Research Committee, Semnan University of Medical Sciences, Semnan 3514799442, Iran"},{"name":"Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5088-3791","authenticated-orcid":false,"given":"Valentyn","family":"Oksenych","sequence":"additional","affiliation":[{"name":"Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-4943","authenticated-orcid":false,"given":"Dariush","family":"Haghmorad","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan 3514799442, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s40588-023-00213-6","article-title":"Gut microbiota and autoimmune diseases: Mechanisms, treatment, challenges, and future recommendations","volume":"11","author":"Heravi","year":"2024","journal-title":"Curr. 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