{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:04:59Z","timestamp":1792389899313,"version":"4.4.0"},"reference-count":62,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder marked by inflammation, demyelination, and neuronal loss within the central nervous system. Despite advances in diagnostics, current tools remain insufficiently sensitive and specific. Metabolomics has emerged as a promising approach to explore MS pathophysiology and discover novel biomarkers. This PRISMA-guided systematic review included 29 original studies using validated metabolomic techniques in adult patients with MS. Biological samples analyzed included serum, cerebrospinal fluid, and feces. Consistent metabolic alterations were identified across several pathways. The kynurenine pathway demonstrated a shift toward neurotoxic metabolites, alongside reductions in microbial-derived indoles, indicating inflammation and gut dysbiosis. Energy metabolism was impaired, with changes in glycolysis, tricarboxylic acid (TCA) cycle, and mitochondrial function. Lipid metabolism showed widespread dysregulation involving phospholipids, sphingolipids, endocannabinoids, and polyunsaturated fatty acids, some modulated by treatments such as ocrelizumab and interferon-\u03b2. Nitrogen metabolism was also affected, including amino acids, peptides, and nucleotides. Non-classical and xenobiotic metabolites, such as myo-inositol, further reflected host\u2013microbiome\u2013environment interactions. Several studies demonstrated the potential of metabolomics-based machine learning to distinguish MS subtypes. These findings highlight the value of metabolomics for biomarker discovery and support its integration into personalized therapeutic strategies in MS.<\/jats:p>","DOI":"10.3390\/ijms26189207","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:04:44Z","timestamp":1758546284000},"page":"9207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Metabolomics in Multiple Sclerosis: Advances, Challenges, and Clinical Perspectives\u2014A Systematic Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8866-3680","authenticated-orcid":false,"given":"Jan","family":"Smusz","sequence":"first","affiliation":[{"name":"Department of Neurology, University Clinical Hospital in Bialystok, Marii Sk\u0142odowskiej-Curie 24A, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2879-9710","authenticated-orcid":false,"given":"Patrycja","family":"Mojsak","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Laboratory, Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Matys","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Clinical Hospital in Bialystok, Marii Sk\u0142odowskiej-Curie 24A, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Miro\u0144czuk","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Clinical Hospital in Bialystok, Marii Sk\u0142odowskiej-Curie 24A, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Tarasiuk","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Clinical Hospital in Bialystok, Marii Sk\u0142odowskiej-Curie 24A, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-6397","authenticated-orcid":false,"given":"Kamil","family":"Grubczak","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Waszyngtona 13, 15-269 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1084-5747","authenticated-orcid":false,"given":"Aleksandra","family":"Starosz","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Waszyngtona 13, 15-269 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kochanowicz","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Clinical Hospital in Bialystok, Marii Sk\u0142odowskiej-Curie 24A, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Ku\u0142akowska","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Clinical Hospital in Bialystok, Marii Sk\u0142odowskiej-Curie 24A, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Ruszczy\u0144ska","sequence":"additional","affiliation":[{"name":"Klinika Bocian Fertility Clinic, ul. Akademicka 26, 15-267 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kapica-Topczewska","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Clinical Hospital in Bialystok, Marii Sk\u0142odowskiej-Curie 24A, 15-276 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy","volume":"19","author":"Ghasemi","year":"2017","journal-title":"Cell J."},{"key":"ref_2","first-page":"e33242","article-title":"An Overview of the History, Pathophysiology, and Pharmacological Interventions of Multiple Sclerosis","volume":"15","author":"Dighriri","year":"2023","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","article-title":"Multiple Sclerosis Pathology","volume":"8","author":"Lassmann","year":"2018","journal-title":"Cold Spring Harb. 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