{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:41:23Z","timestamp":1776919283229,"version":"3.51.2"},"reference-count":110,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck Serono Ltd., an affiliate of Merck KGaA.","award":["na"],"award-info":[{"award-number":["na"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interactions between the gut microbiota, immune system, and brain seem to be involved in the pathogenesis and disease activity of multiple sclerosis (MS). Some MS disease-modifying therapies (DMTs) have been shown to alter the microbiota, but whether this is related to their specific mode of action or indirectly related to their immune-modulatory effect is unknown. In this longitudinal study, we characterized the effects of two DMTs on the microbiota under similar conditions and populations: the injectable, moderate-efficacy DMT interferon beta-1a (INF\u03b2-1a) and the oral, high-efficacy DMT cladribine tablets (CladT). Taxonomic differences were identified following 6 months of therapy for each DMT, and both were associated with the elevation of short-chain fatty acid (SCFA) producers from the Lachnospiraceae, Lactobacillaceae, and Ruminococcaceae families (Firmicutes), while members of Bacteroidetes and Proteobacteria were reduced. Moreover, a higher abundance of Alphaproteobacteria and Betaproteobacteria at baseline was associated with disease activity within 1\u20132 years of follow-up, while a higher abundance of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae, and Streptococcaceae microbes, among others, was associated with no evidence of disease activity (NEDA). Our results provide supporting evidence that alteration of the microbiota by DMTs is part of their beneficial effect, and while some modifications seem to be DMT-specific, MS-DMTs in general promote SCFA-producing microbes, which positively correlate with a favorable clinical outcome. Future therapeutic strategies for PwMS may benefit from microbiome modulation, contingent upon additional mechanistic and interventional studies.<\/jats:p>","DOI":"10.3390\/ijms27083500","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:24:58Z","timestamp":1776176698000},"page":"3500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunotherapy-Mediated Modulation of the Gut Microbiota in Multiple Sclerosis: The Effects of High-Efficacy (Cladribine) and Moderate-Efficacy (Interferon Beta-1a) Treatments"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9620-5255","authenticated-orcid":false,"given":"Elsebeth","family":"Staun-Ram","sequence":"first","affiliation":[{"name":"Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"},{"name":"Neuroimmunology Unit & Multiple Sclerosis Center, Lady Davis Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anat","family":"Volkowich","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit & Multiple Sclerosis Center, Lady Davis Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Glass-Marmor","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit & Multiple Sclerosis Center, Lady Davis Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5843-6841","authenticated-orcid":false,"given":"Ariel","family":"Miller","sequence":"additional","affiliation":[{"name":"Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"},{"name":"Neuroimmunology Unit & Multiple Sclerosis Center, Lady Davis Carmel Medical Center, Haifa 3436212, Israel"},{"name":"Department of Neurology, Lady Davis Carmel Medical Center, Haifa 3436212, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s13311-017-0588-x","article-title":"The \u201cGut Feeling\u201d: Breaking Down the Role of Gut Microbiome in Multiple Sclerosis","volume":"15","author":"Freedman","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"k2179","DOI":"10.1136\/bmj.k2179","article-title":"Role of the gut microbiota in nutrition and health","volume":"361","author":"Valdes","year":"2018","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.copbio.2015.08.015","article-title":"Pathways and Functions of Gut Microbiota Metabolism Impacting Host Physiology","volume":"36","author":"Krishnan","year":"2015","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Abele, G., Miggiano, D., Gasbarrini, A., and Mele, M.C. (2019). What is the healthy gut microbiota composition ? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 10.","DOI":"10.3390\/microorganisms7010014"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Elsayed, N.S., Aston, P., Bayanagari, V.R., and Shukla, S.K. (2022). The gut microbiome molecular mimicry piece in the multiple sclerosis puzzle. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.972160"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Del Negro, I., Pez, S., Varsace, S., Marziali, A., Gigli, G., Tereshko, Y., and Valente, M. (2024). Impact of Disease-Modifying Therapies on Gut\u2014Brain Axis in Multiple Sclerosis. Medicina, 60.","DOI":"10.3390\/medicina60010006"},{"key":"ref_7","first-page":"29","article-title":"Microbiota-Gut-Brain axis and its therapeutic applications in neurodegenerative diseases","volume":"9","author":"Loh","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Parodi, B., and De Rosbo, N.K. (2021). The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.718220"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12015","DOI":"10.1038\/ncomms12015","article-title":"Alterations of the human gut microbiome in multiple sclerosis","volume":"7","author":"Jangi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16396","DOI":"10.1038\/s41598-019-52894-z","article-title":"Gut microbiome of treatment-na\u00efve MS patients of different ethnicities early in disease course","volume":"9","author":"Ventura","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28484","DOI":"10.1038\/srep28484","article-title":"Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/s41582-022-00697-8","article-title":"The role of the gut microbiota in multiple sclerosis","volume":"18","author":"Correale","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Galluzzo, P., Capri, F.C., Vecchioni, L., Realmuto, S., Scalisi, L., Cottone, S., Nuzzo, D., and Alduina, R. (2021). Comparison of the intestinal microbiome of italian patients with multiple sclerosis and their household relatives. Life, 11.","DOI":"10.3390\/life11070620"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/s11940-015-0344-7","article-title":"The Gut Microbiome in Multiple Sclerosis","volume":"17","author":"Mielcarz","year":"2015","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101427","DOI":"10.1016\/j.msard.2019.101427","article-title":"The multiple sclerosis gut microbiota: A systematic review","volume":"37","author":"Mirza","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108380","DOI":"10.1016\/j.clim.2020.108380","article-title":"Gut dysbiosis and multiple sclerosis","volume":"235","author":"Noto","year":"2022","journal-title":"Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ordo\u00f1ez-Rodriguez, A., Roman, P., Rueda-Ruzafa, L., Campos-Rios, A., and Cardona, D. (2023). Changes in gut microbiota and Multiple Sclerosis: A systematic review. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20054624"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nitzan, Z., Staun-Ram, E., Volkowich, A., and Miller, A. (2023). Multiple Sclerosis-Associated Gut Microbiome in the Israeli Diverse Populations: Associations with Ethnicity, Gender, Disability Status, Vitamin D Levels, and Mediterranean Diet. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241915024"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15292","DOI":"10.1038\/s41598-024-64369-x","article-title":"Identification of commensal gut microbiota signatures as predictors of clinical severity and disease progression in multiple sclerosis","volume":"14","author":"Montgomery","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102055","DOI":"10.1016\/j.xcrm.2025.102055","article-title":"Gut microbiota and metabolites are linked to disease progression in multiple sclerosis","volume":"6","author":"Schwerdtfeger","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jns.2016.02.042","article-title":"Gut microbiota composition and relapse risk in pediatric MS: A pilot study","volume":"363","author":"Tremlett","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1002\/acn3.51441","article-title":"Gut microbiome is associated with multiple sclerosis activity in children","volume":"8","author":"Horton","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1111\/cts.13381","article-title":"Bringing pharmacomicrobiomics to the clinic through well-designed studies","volume":"15","author":"Steiner","year":"2022","journal-title":"Clin. Transl. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"578087","DOI":"10.1016\/j.jneuroim.2023.578087","article-title":"The role of multiple sclerosis therapies on the dynamic of human gut microbiota","volume":"378","author":"Vacaras","year":"2023","journal-title":"J. Neuroimmunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1007\/s00415-023-12107-0","article-title":"Disease-modifying therapies used to treat multiple sclerosis and the gut microbiome: A systematic review","volume":"271","author":"Tsai","year":"2023","journal-title":"J. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/JIM.0000000000000192","article-title":"Gut microbiota in multiple sclerosis: Possible influence of immunomodulators","volume":"63","author":"Cantarel","year":"2015","journal-title":"J. Investig. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e517","DOI":"10.1212\/NXI.0000000000000517","article-title":"Disease-modifying therapies alter gut microbial composition in MS","volume":"6","author":"Zhu","year":"2019","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_28","first-page":"17562864241306564","article-title":"Immunotherapy-mediated modulation of the gut microbiota in multiple sclerosis and associations with diet and clinical response\u2014The effect of dimethyl fumarate therapy","volume":"18","author":"Volkowich","year":"2025","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_29","first-page":"2055217319888767","article-title":"Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis\u2014A pilot trial","volume":"5","author":"Myhr","year":"2019","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2147055","DOI":"10.1080\/19490976.2022.2147055","article-title":"Gut microbiota composition as a candidate risk factor for dimethyl fumarate-induced lymphopenia in multiple sclerosis","volume":"14","author":"Diebold","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1016\/j.cell.2022.08.021","article-title":"Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course","volume":"185","author":"Zhou","year":"2022","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ferri, C., Castellazzi, M., Merli, N., Laudisi, M., Baldin, E., Baldi, E., Mancabelli, L., Ventura, M., and Pugliatti, M. (2023). Gut Microbiota Changes during Dimethyl Fumarate Treatment in Patients with Multiple Sclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032720"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s00415-023-11969-8","article-title":"Multiple sclerosis: Time for early treatment with high\u2014Efficacy drugs","volume":"271","author":"Selmaj","year":"2024","journal-title":"J. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s40265-023-01942-0","article-title":"Escalation Versus Induction\/High\u2014Efficacy Treatment Strategies for Relapsing Multiple Sclerosis: Which is Best for Patients?","volume":"83","author":"Edan","year":"2023","journal-title":"Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/MIB.0000000000001078","article-title":"Type 1 Interferon in the Human Intestine\u2014A Co-ordinator of the Immune Response to the Microbiota","volume":"23","author":"Giles","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kozhieva, M., Naumova, N., Alikina, T., Boyko, A., Vlassov, V., and Kabilov, M.R. (2021). The Core of Gut Life: Firmicutes Profile in Patients with Relapsing-Remitting Multiple Sclerosis. Life, 11.","DOI":"10.3390\/life11010055"},{"key":"ref_37","first-page":"495","article-title":"The influence of interferon \u03b2-1b on gut microbiota composition in patients with multiple sclerosis","volume":"36","author":"Oteo","year":"2021","journal-title":"Neurolog\u00eda"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106","DOI":"10.15698\/mic2024.04.819","article-title":"The effect of multiple sclerosis therapy on gut microbiota dysbiosis: A longitudinal prospective study","volume":"11","author":"Paraschiv","year":"2024","journal-title":"Microb. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"van Pamelen, J., Rodriguez-Mogeda, C., van Olst, L., van der Pol, S.M.A., Boon, M.L., De Beukelaar, J., Gerlach, O.H.H., Budding, A.E., Killestein, J., and De Vries, H.E. (2025). The gut-brain-axis one year after treatment with cladribine tablets in patients with relapsing remitting multiple sclerosis: A pilot study. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1514762"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40793-020-00358-7","article-title":"Tax4Fun2: Prediction of habitat-specific functional profiles and functional redundancy based on 16S rRNA gene sequences","volume":"7","author":"Wemheuer","year":"2020","journal-title":"Environ. Microbiomes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41596-019-0264-1","article-title":"Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data","volume":"15","author":"Chong","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nature10554","article-title":"Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination\u2014With comments","volume":"479","author":"Berer","year":"2011","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10719","DOI":"10.1073\/pnas.1711233114","article-title":"Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice","volume":"114","author":"Berer","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1073\/pnas.1711235114","article-title":"Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models","volume":"114","author":"Cekanaviciute","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Laeeq, T., Vongsavath, T., and Tun, K.M. (2023). The Potential Role of Fecal Microbiota Transplant in the Reversal or Stabilization of Multiple Sclerosis Symptoms: A Literature Review on Efficacy and Safety. Microorganisms, 11.","DOI":"10.3390\/microorganisms11122840"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1039\/D0FO03203D","article-title":"Efficacy of probiotics in multiple sclerosis: A systematic review of preclinical trials and meta-analysis of randomized controlled trials","volume":"12","author":"Jiang","year":"2021","journal-title":"Food Funct."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18577","DOI":"10.1038\/s41598-023-46047-6","article-title":"The effect of probiotic supplementation on the clinical and para-clinical findings of multiple sclerosis: A randomized clinical trial","volume":"13","author":"Asghari","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.maturitas.2018.03.012","article-title":"Microbiota\u2013drug interactions: Impact on metabolism and efficacy of therapeutics","volume":"112","author":"Wilkinson","year":"2018","journal-title":"Maturitas"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"106792","DOI":"10.1016\/j.jsbmb.2025.106792","article-title":"Microbial modulation of digoxin bioavailability: A pharmacomicrobiome perspective on Eggerthella lenta\u2019s role in steroid-like drug metabolism and precision therapeutics","volume":"252","author":"Ganamurali","year":"2025","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1126\/science.1235872","article-title":"Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta","volume":"341","author":"Haiser","year":"2013","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3728","DOI":"10.1038\/s41598-022-07336-8","article-title":"B-cell-depletion reverses dysbiosis of the microbiome in multiple sclerosis patients","volume":"12","author":"Troci","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/ana.26084","article-title":"Gut Microbiome in Progressive Multiple Sclerosis","volume":"89","author":"Cox","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1002\/acn3.51476","article-title":"The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes","volume":"8","author":"Tremlett","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bui, T.N.Y., Paul, A., Guleria, S., Sullivan, J.M.O., and Toldi, G. (2025). Short-chain fatty acids\u2014A key link between the gut microbiome and T-lymphocytes in neonates?. Pediatr. Res., 1\u20139.","DOI":"10.1038\/s41390-025-04075-0"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2274126","DOI":"10.1080\/19490976.2023.2274126","article-title":"Targeting gut microbiota: New therapeutic opportunities in multiple sclerosis","volume":"15","author":"Kujawa","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"108379","DOI":"10.1016\/j.clim.2020.108379","article-title":"Role of diet in regulating the gut microbiota and multiple sclerosis","volume":"235","author":"Sanchez","year":"2022","journal-title":"Clin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.immuni.2015.09.007","article-title":"Dietary fatty acids directly impact Central Nervous System autoimmunity via the small intestine","volume":"43","author":"Haghikia","year":"2015","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"114763","DOI":"10.1016\/j.biopha.2023.114763","article-title":"Biomedicine & Pharmacotherapy Short chain fatty acids, a possible treatment option for autoimmune diseases","volume":"163","author":"Golpour","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s40120-023-00565-7","article-title":"Twenty Years of Subcutaneous Interferon-Beta-1a for Multiple Sclerosis: Contemporary Perspectives","volume":"13","author":"Freedman","year":"2024","journal-title":"Neurol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.tim.2022.01.007","article-title":"Microbiota regulation of viral infections through interferon signaling","volume":"30","author":"Wirusanti","year":"2022","journal-title":"Trends Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.neuron.2018.01.021","article-title":"Multiple Sclerosis: Mechanisms and Immunotherapy","volume":"97","author":"Kaskow","year":"2018","journal-title":"Neuron"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/ni.3345","article-title":"Apoptotic epithelial cells control the abundance of T reg cells at barrier surfaces","volume":"17","author":"Gamage","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/ana.20161","article-title":"Interferon-beta stabilizes barrier characteristics of brain endothelial cells in vitro","volume":"56","author":"Kraus","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Boziki, M.K., Kesidou, E., Theotokis, P., Mentis, A.A., Karafoulidou, E., and Melnikov, M. (2020). brain sciences Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know. Brain Sci., 10.","DOI":"10.3390\/brainsci10040234"},{"key":"ref_65","first-page":"200","article-title":"Cathepsins (S and B) and their inhibitor Cystatin C in immune cells: Modulation by interferon-beta and role played in cell migration","volume":"232","author":"Miller","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2147\/BTT.S489523","article-title":"Short and Medium Chain Fatty Acids in a Cohort of Na\u00efve Multiple Sclerosis Patients: Pre- and Post- Interferon Beta Treatment Assessment","volume":"18","author":"Barcutean","year":"2024","journal-title":"Biol. Targets Ther."},{"key":"ref_67","first-page":"10.1128","article-title":"Bifidobacteria and Their Health-Promoting Effects","volume":"5","author":"Delgado","year":"2017","journal-title":"Microbiol. Spectr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"36","DOI":"10.20517\/mrr.2023.37","article-title":"Bifidobacterium and the intestinal mucus layer","volume":"2","author":"Gutierrez","year":"2023","journal-title":"Microbiome Res. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e2413953122","DOI":"10.1073\/pnas.2413953122","article-title":"Specific microbial ratio in the gut microbiome is associated with multiple sclerosis","volume":"122","author":"Ghimire","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"103931","DOI":"10.1016\/j.msard.2022.103931","article-title":"Immunological consequences of cladribine treatment in multiple sclerosis: A real-world study","volume":"64","author":"Rolfes","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e200048","DOI":"10.1212\/NXI.0000000000200048","article-title":"Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy","volume":"10","author":"Wiendl","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1007\/s00415-025-13530-1","article-title":"Is therapy-free remission a realistic goal with cladribine tablets in multiple sclerosis? New insights into the mechanism of action and clinical implications of immune reconstitution with cladribine tablets in MS therapy","volume":"272","author":"Kleinschnitz","year":"2025","journal-title":"J. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wiendl, H., Barkhof, F., Montalban, X., Achiron, A., Derfuss, T., and Chan, A. (2025). Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: Results of the 2-year MAGNIFY-MS study. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1512189"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ford, R.K., Juillard, P., Hawke, S., Grau, G.E., and Marsh-wakefield, F. (2022). Cladribine Reduces Trans-Endothelial Migration of Memory T Cells across an In Vitro Blood\u2014Brain Barrier. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206006"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Bronzini, M., Maglione, A., Rosso, R., Matta, M., Masuzzo, F., Rolla, S., and Clerico, M. (2023). Feeding the gut microbiome: Impact on multiple sclerosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1176016"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Dziedzic, A., and Saluk, J. (2022). Probiotics and Commensal Gut Microbiota as the Effective Alternative Therapy for Multiple Sclerosis Patients Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214478"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wrzosek, L., Miquel, S., Noordine, M.L., Bouet, S., Chevalier-Curt, M.J., Robert, V., Philippe, C., Bridonneau, C., Cherbuy, C., and Robbe-Masselot, C. (2013). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol., 11.","DOI":"10.1186\/1741-7007-11-61"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Miyake, S., Kim, S.S.W.S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., and Kim, S.S.W.S. (2015). Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to clostridia XIVa and IV clusters. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137429"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Chen, B., Zhang, X., Akbar, M.T., Wu, T., Zhang, Y., Zhi, L., and Shen, Q. (2024). Exploration of the Muribaculaceae Family in the Gut Microbiota: Diversity, Metabolism, and Function. Nutrients, 16.","DOI":"10.3390\/nu16162660"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"59915","DOI":"10.18632\/oncotarget.18346","article-title":"The regulation of immune cells by Lactobacilli: A potential therapeutic target for anti-atherosclerosis therapy","volume":"8","author":"Ding","year":"2017","journal-title":"Oncotarget"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Rastogi, S., and Singh, A. (2022). Gut microbiome and human health: Exploring how the probiotic genus Lactobacillus modulate immune responses. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1042189"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.clim.2013.01.001","article-title":"Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response","volume":"146","author":"Kwon","year":"2013","journal-title":"Clin. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zangeneh, Z., Rostamin, M., Motamedi, H., Alvandi, A., and Abiri, R. (2025). The potential effectiveness of probiotics in reducing multiple sclerosis progression in preclinical and clinical studies: A worldwide systematic review and meta-analysis. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0319755"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1943289","DOI":"10.1080\/19490976.2021.1943289","article-title":"Probiotic and commensal gut microbial therapies in multiple sclerosis and its animal models: A comprehensive review","volume":"13","author":"Blais","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/ana.25244","article-title":"A probiotic modulates the microbiome and immunity in multiple sclerosis","volume":"83","author":"Tankou","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Golan, D., Halhal, B., Glass-Marmor, L., Staun-Ram, E., Rozenberg, O., Lavi, I., Dishon, S., Barak, M., Ish-Shalom, S., and Miller, A. (2013). Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: A randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties. BMC Neurol., 13.","DOI":"10.1186\/1471-2377-13-60"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jneuroim.2017.02.007","article-title":"TRPV1 polymorphisms and risk of interferon \u03b2-induced flu-like syndrome in patients with relapsing-remitting multiple sclerosis","volume":"305","author":"Buttari","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.2174\/1570159X19666211101142115","article-title":"Interferon-Beta Injection in Multiple Sclerosis Patients Related to the In- duction of Headache and Flu-Like Pain Symptoms: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"20","author":"Pereira","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1179\/1476830514Y.0000000117","article-title":"The association of diet with quality of life, disability, and relapse rate in an international sample of people with multiple sclerosis","volume":"18","author":"Hadgkiss","year":"2015","journal-title":"Nutr. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41575-021-00512-7","article-title":"Leveraging diet to engineer the gut microbiome","volume":"18","author":"Wolter","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"D\u017eidi\u0107 Krivi\u0107, A., Begagi\u0107, E., Had\u017ei\u0107, S., Be\u0107irovi\u0107, A., Be\u0107irovi\u0107, E., Hibi\u0107, H., Tandir Lihi\u0107, L., Kadi\u0107 Vukas, S., Be\u010duli\u0107, H., and Kasapovi\u0107, T. (2025). Unveiling the Important Role of Gut Microbiota and Diet in Multiple Sclerosis. Brain Sci., 15.","DOI":"10.3390\/brainsci15030253"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"55","DOI":"10.7224\/1537-2073.2013-006","article-title":"Nurses \u2019 Perspective on Approaches to Limit Flu-Like Symptoms During Interferon Therapy for Multiple Sclerosis","volume":"16","author":"Filipi","year":"2014","journal-title":"Int. J. MS Care"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41522-019-0097-2","article-title":"Transfusional iron overload and intravenous iron infusions modify the mouse gut microbiota similarly to dietary iron","volume":"5","author":"Wojczyk","year":"2019","journal-title":"Biofilms Microbiomes"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Nemati, M.H., Yazdanpanah, E., Kazemi, R., Orooji, N., Dadfar, S., Oksenych, V., and Haghmorad, D. (2025). Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential. Biology, 14.","DOI":"10.3390\/biology14040435"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Boussamet, L., Rajoka, M.S.R., and Berthelot, L. (2022). Microbiota, IgA and Multiple Sclerosis. Microorganisms, 10.","DOI":"10.3390\/microorganisms10030617"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"eabc7191","DOI":"10.1126\/sciimmunol.abc7191","article-title":"Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis","volume":"5","author":"Zhou","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.cell.2019.03.037","article-title":"Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10","volume":"177","author":"Rojas","year":"2019","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e997","DOI":"10.1212\/NXI.0000000000000997","article-title":"Perturbed microbiota\/immune homeostasis in multiple sclerosis","volume":"8","author":"Sterlin","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Takeuchi, T., and Ohno, H. (2022). IgA in human health and diseases: Potential regulator of commensal microbiota. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1024330"},{"key":"ref_100","first-page":"20552173221149688","article-title":"The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis","volume":"9","author":"Lycett","year":"2023","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1016\/j.clnu.2018.12.034","article-title":"Adaptation and predictive utility of a Mediterranean diet screener score","volume":"38","author":"Endevelt","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.3945\/jn.110.135566","article-title":"A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women","volume":"141","author":"Estruch","year":"2011","journal-title":"J. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Gonz\u00e1lez, M.A., Garc\u00eda-Arellano, A., Toledo, E., Salas-Salvad\u00f3, J., Buil-Cosiales, P., Corella, D., Covas, M.I., Schr\u00f6der, H., Ar\u00f3s, F., and G\u00f3mez-Gracia, E. (2012). A 14-item mediterranean diet assessment tool and obesity indexes among high-risk subjects: The PREDIMED trial. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043134"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1023\/A:1025634020718","article-title":"Development of a semi-quantitative Food Frequency Questionnaire (FFQ) to assess dietary intake of multiethnic populations","volume":"18","author":"Shahar","year":"2003","journal-title":"Eur. J. Epidemiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/jn\/135.3.573","article-title":"DEARR study Dietary evaluation and attenuation of relative risk: Multiple comparisons between blood and urinary biomarkers, food frequency, and 24-h recall questionnaires: The DEARR study","volume":"135","author":"Shai","year":"2005","journal-title":"J. Nutr."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1079\/PHN2002445","article-title":"Adaptation of international nutrition databases and data-entry system tools to a specific population","volume":"6","author":"Shai","year":"2003","journal-title":"Public Health Nutr."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"W180","DOI":"10.1093\/nar\/gkx295","article-title":"MicrobiomeAnalyst: A web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data","volume":"45","author":"Dhariwal","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"W310","DOI":"10.1093\/nar\/gkad407","article-title":"MicrobiomeAnalyst 2.0: Comprehensive statistical, functional and integrative analysis of microbiome data","volume":"51","author":"Lu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41467-022-28034-z","article-title":"Microbiome differential abundance methods produce different results across 38 datasets","volume":"13","author":"Nearing","year":"2022","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:12:31Z","timestamp":1776917551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":110,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083500"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083500","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]}}}