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It is associated with degeneration and demyelination of the myelin sheath around the nerves, resulting in multiple neurological disability symptoms ranging from mild to severe cases that end with paralysis sometimes. MS is one of the rising diseases globally that is unfortunately associated with reduced quality of life and adding national economic burdens. The definite MS mechanism is not clearly defined; however, all the previous researches confirm the role of the\u00a0immune system as the master contributor in the pathogenesis. Innate and adaptive immune cells are activated peripherally then attracted toward the central nervous system (CNS) due to the breakdown of the blood\u2013brain barrier. Recently, the gut-brain axis was shown to depend on gut metabolites that are produced by different microorganisms in the colon. The difference in microbiota composition between individuals is responsible for diversity in secreted metabolites that affect immune responses locally in the gut or systemically when reach blood circulation to the brain. It may enhance or suppress immune responses in the\u00a0central nervous system (CNS) (repeated short forms); consequently, it may exacerbate or ameliorate MS symptoms. Recent data showed that some metabolites can be used as adjuvant therapy in MS and other inflammatory diseases. This review sheds light on the nature of MS and the possible interaction between gut microbiota and immune system regulation through the gut-brain axis, hence contributing to MS pathogenesis.\n<\/jats:p>","DOI":"10.1007\/s12035-025-04728-5","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T19:09:33Z","timestamp":1739300973000},"page":"7762-7775","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multiple Sclerosis: A Story of the\u00a0Interaction Between Gut Microbiome and Components of the\u00a0Immune System"],"prefix":"10.1007","volume":"62","author":[{"given":"Esraa","family":"Mohsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham","family":"Haffez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selwan","family":"Hamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taghrid S.","family":"El-Mahdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"4728_CR1","doi-asserted-by":"publisher","first-page":"672346","DOI":"10.3389\/fimmu.2021.672346","volume":"12","author":"Y Zhang","year":"2021","unstructured":"Zhang Y et al (2021) Toll-like receptors gene polymorphisms in autoimmune disease. 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