Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system atrophy. Microbiota dysbiosis is implicated in MS pathogenesis and treatment outcomes. In our study, we observed microbiota changes already present in treatment-naïve individuals with clinically isolated syndrome, affecting both bacteria and viruses. Gut bacteria alterations were transient during the first 12 months of anti-CD20 therapy. After 12 months, responders showed increased gut microbiota alpha diversity approaching healthy control levels, while non-responders showed a significant decline. Key changes involved Parabacteroides spp., producers of short-chain fatty acids that support gut barrier function and have anti-inflammatory potential. We detected altered gut barrier biomarkers and antibodies against common commensals in MS patients, which were modulated by anti-CD20 treatment. Notably, lipopolysaccharide-binding protein and mannose-binding lectin decreased only in responders. These findings suggest that intestinal barrier damage contributes to immune responses linked to microbial translocation, MS pathogenesis, and treatment outcomes.

Department of Genetics and Microbiology Faculty of Science Charles University BIOCEV Vestec Czech Republic

Department of Neurology and Centre of Clinical Neuroscience 1st Medical Faculty Charles University and General Medical Hospital Prague Prague Czech Republic

Laboratory of Animal Evolutionary Biology Faculty of Science Department of Zoology Charles University Prague Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Gnotobiology Institute of Microbiology of the Czech Academy of Sciences Novy Hradek Czech Republic

Zobrazit více v PubMed

Thompson A.J., Baranzini S.E., Geurts J., Hemmer B., Ciccarelli O. Multiple sclerosis. Lancet. 2018;391:1622–1636. doi: 10.1016/S0140-6736(18)30481-1. PubMed DOI

Cekanaviciute E., Yoo B.B., Runia T.F., Debelius J.W., Singh S., Nelson C.A., Kanner R., Bencosme Y., Lee Y.K., Hauser S.L., et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl. Acad. Sci. USA. 2017;114:10713–10718. doi: 10.1073/pnas.1711235114. PubMed DOI PMC

Tlaskalová-Hogenová H., Stěpánková R., Kozáková H., Hudcovic T., Vannucci L., Tučková L., Rossmann P., Hrnčíř T., Kverka M., Zákostelská Z., et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell. Mol. Immunol. 2011;8:110–120. doi: 10.1038/cmi.2010.67. PubMed DOI PMC

Lee Y.K., Menezes J.S., Umesaki Y., Mazmanian S.K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA. 2011;108:4615–4622. doi: 10.1073/pnas.1000082107. PubMed DOI PMC

Berer K., Mues M., Koutrolos M., Rasbi Z.A., Boziki M., Johner C., Wekerle H., Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479:538–541. doi: 10.1038/nature10554. PubMed DOI

Ordonez-Rodriguez A., Roman P., Rueda-Ruzafa L., Campos-Rios A., Cardona D. Changes in Gut Microbiota and Multiple Sclerosis: A Systematic Review. Int. J. Environ. Res. Public Health. 2023;20 doi: 10.3390/ijerph20054624. PubMed DOI PMC

Ochoa-Reparaz J., Magori K., Kasper L.H. The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis. Ann. Transl. Med. 2017;5:145. doi: 10.21037/atm.2017.01.18. PubMed DOI PMC

Bjornevik K., Cortese M., Healy B.C., Kuhle J., Mina M.J., Leng Y., Elledge S.J., Niebuhr D.W., Scher A.I., Munger K.L., Ascherio A. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022;375:296–301. doi: 10.1126/science.abj8222. PubMed DOI

Lanz T.V., Brewer R.C., Ho P.P., Moon J.-S., Jude K.M., Fernandez D., Fernandes R.A., Gomez A.M., Nadj G.-S., Bartley C.M., et al. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Nature. 2022;603:321–327. doi: 10.1038/s41586-022-04432-7. PubMed DOI PMC

Pender M.P., Csurhes P.A., Smith C., Douglas N.L., Neller M.A., Matthews K.K., Beagley L., Rehan S., Crooks P., Hopkins T.J., et al. Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis. JCI Insight. 2020;5 doi: 10.1172/jci.insight.144624. PubMed DOI PMC

Hauser S.L., Bar-Or A., Comi G., Giovannoni G., Hartung H.P., Hemmer B., Lublin F., Montalban X., Rammohan K.W., Selmaj K., et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N. Engl. J. Med. 2017;376:221–234. doi: 10.1056/NEJMoa1601277. PubMed DOI

Ellwardt E., Rolfes L., Klein J., Pape K., Ruck T., Wiendl H., Schroeter M., Zipp F., Meuth S.G., Warnke C., Bittner S. Ocrelizumab initiation in patients with MS: A multicenter observational study. Neurol. Neuroimmunol. Neuroinflamm. 2020;7 doi: 10.1212/NXI.0000000000000719. PubMed DOI PMC

Montalban X., Hauser S.L., Kappos L., Arnold D.L., Bar-Or A., Comi G., de Seze J., Giovannoni G., Hartung H.P., Hemmer B., et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N. Engl. J. Med. 2017;376:209–220. doi: 10.1056/NEJMoa1606468. PubMed DOI

Katz Sand I., Zhu Y., Ntranos A., Clemente J.C., Cekanaviciute E., Brandstadter R., Crabtree-Hartman E., Singh S., Bencosme Y., Debelius J., et al. Disease-modifying therapies alter gut microbial composition in MS. Neurol. Neuroimmunol. Neuroinflamm. 2019;6 doi: 10.1212/NXI.0000000000000517. PubMed DOI PMC

Coufal S., Kverka M., Kreisinger J., Thon T., Rob F., Kolar M., Reiss Z., Schierova D., Kostovcikova K., Roubalova R., et al. Serum TGF-beta1 and CD14 Predicts Response to Anti-TNF-alpha Therapy in IBD. J. Immunol. Res. 2023;2023 doi: 10.1155/2023/1535484. PubMed DOI PMC

Bajer L., Kverka M., Kostovcik M., Macinga P., Dvorak J., Stehlikova Z., Brezina J., Wohl P., Spicak J., Drastich P. Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World J. Gastroenterol. 2017;23:4548–4558. doi: 10.3748/wjg.v23.i25.4548. PubMed DOI PMC

Mochol M., Taubøll E., Aukrust P., Ueland T., Andreassen O.A., Svalheim S. Interleukin 18 (IL-18) and its binding protein (IL-18BP) are increased in patients with epilepsy suggesting low-grade systemic inflammation. Seizure. 2020;80:221–225. doi: 10.1016/j.seizure.2020.05.018. PubMed DOI

Preiningerova J.L., Jiraskova Zakostelska Z., Srinivasan A., Ticha V., Kovarova I., Kleinova P., Tlaskalova-Hogenova H., Kubala Havrdova E. Multiple Sclerosis and Microbiome. Biomolecules. 2022;12 doi: 10.3390/biom12030433. PubMed DOI PMC

iMSMS Consortium Electronic address sergio baranzini@ucsf edu. iMSMS Consortium Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course. Cell. 2022;185:3467–3486.e16. doi: 10.1016/j.cell.2022.08.021. PubMed DOI PMC

Cox L.M., Maghzi A.H., Liu S., Tankou S.K., Dhang F.H., Willocq V., Song A., Wasén C., Tauhid S., Chu R., et al. Gut Microbiome in Progressive Multiple Sclerosis. Ann. Neurol. 2021;89:1195–1211. doi: 10.1002/ana.26084. PubMed DOI PMC

Jangi S., Gandhi R., Cox L.M., Li N., von Glehn F., Yan R., Patel B., Mazzola M.A., Liu S., Glanz B.L., et al. Alterations of the human gut microbiome in multiple sclerosis. Nat. Commun. 2016;7 doi: 10.1038/ncomms12015. PubMed DOI PMC

Troci A., Zimmermann O., Esser D., Krampitz P., May S., Franke A., Berg D., Leypoldt F., Stürner K.H., Bang C. B-cell-depletion reverses dysbiosis of the microbiome in multiple sclerosis patients. Sci. Rep. 2022;12:3728. doi: 10.1038/s41598-022-07336-8. PubMed DOI PMC

Zeng Q., Junli G., Liu X., Chen C., Sun X., Li H., Zhou Y., Cui C., Wang Y., Yang Y., et al. Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis. Neurochem. Int. 2019;129 doi: 10.1016/j.neuint.2019.104468. PubMed DOI

Notting F., Pirovano W., Sybesma W., Kort R. The butyrate-producing and spore-forming bacterial genus Coprococcus as a potential biomarker for neurological disorders. Gut Microbiome (Camb) 2023;4:e16. doi: 10.1017/gmb.2023.14. PubMed DOI PMC

Lv X., Zhan L., Ye T., Xie H., Chen Z., Lin Y., Cai X., Yang W., Liao X., Liu J., Sun J. Gut commensal Agathobacter rectalis alleviates microglia-mediated neuroinflammation against pathogenesis of Alzheimer disease. iScience. 2024;27 doi: 10.1016/j.isci.2024.111116. PubMed DOI PMC

Schumacher S.M., Doyle W.J., Hill K., Ochoa-Repáraz J. Gut microbiota in multiple sclerosis and animal models. FEBS J. 2025;292:1330–1356. doi: 10.1111/febs.17161. PubMed DOI PMC

Horton M.K., McCauley K., Fadrosh D., Fujimura K., Graves J., Ness J., Wheeler Y., Gorman M.P., Benson L.A., Weinstock-Guttman B., et al. Gut microbiome is associated with multiple sclerosis activity in children. Ann. Clin. Transl. Neurol. 2021;8:1867–1883. doi: 10.1002/acn3.51441. PubMed DOI PMC

Montgomery T.L., Wang Q., Mirza A., Dwyer D., Wu Q., Dowling C.A., Martens J.W.S., Yang J., Krementsov D.N., Mao-Draayer Y. Identification of commensal gut microbiota signatures as predictors of clinical severity and disease progression in multiple sclerosis. Sci. Rep. 2024;14 doi: 10.1038/s41598-024-64369-x. PubMed DOI PMC

Chen J., Chia N., Kalari K.R., Yao J.Z., Novotna M., Paz Soldan M.M., Luckey D.H., Marietta E.V., Jeraldo P.R., Chen X., et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci. Rep. 2016;6 doi: 10.1038/srep28484. PubMed DOI PMC

Lin Q., Dorsett Y., Mirza A., Tremlett H., Piccio L., Longbrake E.E., Choileain S.N., Hafler D.A., Cox L.M., Weiner H.L., et al. Meta-analysis identifies common gut microbiota associated with multiple sclerosis. Genome Med. 2024;16:94. doi: 10.1186/s13073-024-01364-x. PubMed DOI PMC

Vacaras V., Muresanu D.F., Buzoianu A.-D., Nistor C., Vesa S.C., Paraschiv A.-C., Botos-Vacaras D., Vacaras C., Vithoulkas G. The role of multiple sclerosis therapies on the dynamic of human gut microbiota. J. Neuroimmunol. 2023;378 doi: 10.1016/j.jneuroim.2023.578087. PubMed DOI

Ling Z., Cheng Y., Yan X., Shao L., Liu X., Zhou D., Zhang L., Yu K., Zhao L. Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis. Front. Immunol. 2020;11 doi: 10.3389/fimmu.2020.590783. PubMed DOI PMC

Miquel S., Martín R., Rossi O., Bermúdez-Humarán L.G., Chatel J.M., Sokol H., Thomas M., Wells J.M., Langella P. Faecalibacterium prausnitzii and human intestinal health. Curr. Opin. Microbiol. 2013;16:255–261. doi: 10.1016/j.mib.2013.06.003. PubMed DOI

Lopez-Siles M., Duncan S.H., Garcia-Gil L.J., Martinez-Medina M. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics. ISME J. 2017;11:841–852. doi: 10.1038/ismej.2016.176. PubMed DOI PMC

Carlsson A.H., Yakymenko O., Olivier I., Håkansson F., Postma E., Keita A.V., Söderholm J.D. Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis. Scand. J. Gastroenterol. 2013;48:1136–1144. doi: 10.3109/00365521.2013.828773. PubMed DOI

Martin R., Miquel S., Chain F., Natividad J.M., Jury J., Lu J., Sokol H., Theodorou V., Bercik P., Verdu E.F., et al. Faecalibacterium prausnitzii prevents physiological damages in a chronic low-grade inflammation murine model. BMC Microbiol. 2015;15:67. doi: 10.1186/s12866-015-0400-1. PubMed DOI PMC

Weiss G.A., Chassard C., Hennet T. Selective proliferation of intestinal Barnesiella under fucosyllactose supplementation in mice. Br. J. Nutr. 2014;111:1602–1610. doi: 10.1017/S0007114513004200. PubMed DOI

Parker B.J., Wearsch P.A., Veloo A.C.M., Rodriguez-Palacios A. The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health. Front. Immunol. 2020;11:906. doi: 10.3389/fimmu.2020.00906. PubMed DOI PMC

Wu F., Guo X., Zhang J., Zhang M., Ou Z., Peng Y. Phascolarctobacterium faecium abundant colonization in human gastrointestinal tract. Exp. Ther. Med. 2017;14:3122–3126. doi: 10.3892/etm.2017.4878. PubMed DOI PMC

Kim C.H. Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity. Cell. Mol. Immunol. 2023;20:341–350. doi: 10.1038/s41423-023-00987-1. PubMed DOI PMC

Silva A.S., Guimarães J., Sousa C., Mendonça L., Soares-dos-Reis R., Mendonça T., Abreu P., Sequeira L., Sá M.J. Metabolic syndrome parameters and multiple sclerosis disease outcomes: A Portuguese cross-sectional study. Mult. Scler. Relat. Disord. 2023;69 doi: 10.1016/j.msard.2022.104370. PubMed DOI

Gupta V.K., Janda G.S., Pump H.K., Lele N., Cruz I., Cohen I., Ruff W.E., Hafler D.A., Sung J., Longbrake E.E. Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2025;12 doi: 10.1212/NXI.0000000000200355. PubMed DOI PMC

Tremlett H., Zhu F., Arnold D., Bar-Or A., Bernstein C.N., Bonner C., Forbes J.D., Graham M., Hart J., Knox N.C., et al. The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes. Ann. Clin. Transl. Neurol. 2021;8:2252–2269. doi: 10.1002/acn3.51476. PubMed DOI PMC

Schaus S.R., Vasconcelos Periera G., Luis A.S., Madlambayan E., Terrapon N., Ostrowski M.P., Jin C., Hansson G.C., Martens E.C. Ruminococcus torques is a keystone degrader of intestinal mucin glycoprotein, releasing oligosaccharides used by Bacteroides thetaiotaomicron. bioRxiv. 2024 doi: 10.1101/2024.01.15.575725. Preprint at. PubMed DOI PMC

Nishiwaki H., Hamaguchi T., Ito M., Ishida T., Maeda T., Kashihara K., Tsuboi Y., Ueyama J., Shimamura T., Mori H., et al. Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson's Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder. mSystems. 2020;5 doi: 10.1128/mSystems.00797-20. PubMed DOI PMC

Bai D., Zhao J., Wang R., Du J., Zhou C., Gu C., Wang Y., Zhang L., Zhao Y., Lu N. Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier. Acta Pharm. Sin. B. 2024;14:1677–1692. doi: 10.1016/j.apsb.2023.12.015. PubMed DOI PMC

Kang X., Liu C., Ding Y., Ni Y., Ji F., Lau H.C.H., Jiang L., Sung J.J., Wong S.H., Yu J. Roseburia intestinalis generated butyrate boosts anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8(+) T cells. Gut. 2023;72:2112–2122. doi: 10.1136/gutjnl-2023-330291. PubMed DOI PMC

Nie K., Ma K., Luo W., Shen Z., Yang Z., Xiao M., Tong T., Yang Y., Wang X. Roseburia intestinalis: A Beneficial Gut Organism From the Discoveries in Genus and Species. Front. Cell. Infect. Microbiol. 2021;11 doi: 10.3389/fcimb.2021.757718. PubMed DOI PMC

Song L., Sun Q., Zheng H., Zhang Y., Wang Y., Liu S., Duan L. Roseburia hominis Alleviates Neuroinflammation via Short-Chain Fatty Acids through Histone Deacetylase Inhibition. Mol. Nutr. Food Res. 2022;66 doi: 10.1002/mnfr.202200164. PubMed DOI PMC

Jiraskova Zakostelska Z., Kraus M., Coufal S., Prochazkova P., Slavickova Z., Thon T., Hrncir T., Kreisinger J., Kostovcikova K., Kleinova P., et al. Lysate of Parabacteroides distasonis prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response. Front. Immunol. 2024;15 doi: 10.3389/fimmu.2024.1475126. PubMed DOI PMC

Duscha A., Gisevius B., Hirschberg S., Yissachar N., Stangl G.I., Dawin E., Bader V., Haase S., Kaisler J., David C., et al. Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism. Cell. 2020;180:1067–1080.e16. doi: 10.1016/j.cell.2020.02.035. PubMed DOI

Belarbi K., Cuvelier E., Bonte M.-A., Desplanque M., Gressier B., Devos D., Chartier-Harlin M.-C. Glycosphingolipids and neuroinflammation in Parkinson’s disease. Mol. Neurodegener. 2020;15:59. doi: 10.1186/s13024-020-00408-1. PubMed DOI PMC

Albuquerque L.d.S., Damasceno N.R.T., Maia F.N., Carvalho B.M.d., Maia C.S.C., D'Almeida J.A.C., Melo M.L.P.d. Cardiovascular risk estimated in individuals with multiple sclerosis: A case-control study. Mult. Scler. Relat. Disord. 2021;54 doi: 10.1016/j.msard.2021.103133. PubMed DOI

Yang F., Hu T., He K., Ying J., Cui H. Multiple Sclerosis and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study. Front. Immunol. 2022;13 doi: 10.3389/fimmu.2022.861885. PubMed DOI PMC

Bastioli G., Piccirillo S., Graciotti L., Carone M., Sprega G., Taoussi O., Preziuso A., Castaldo P. Calcium Deregulation in Neurodegeneration and Neuroinflammation in Parkinson’s Disease: Role of Calcium-Storing Organelles and Sodium–Calcium Exchanger. Cells. 2024;13:1301. PubMed PMC

Enders M., Heider T., Ludwig A., Kuerten S. Strategies for Neuroprotection in Multiple Sclerosis and the Role of Calcium. Int. J. Mol. Sci. 2020;21 doi: 10.3390/ijms21051663. PubMed DOI PMC

Hundehege P., Epping L., Meuth S. Calcium Homeostasis in Multiple Sclerosis. Neurology International Open. 2017;01:E127–E135. doi: 10.1055/s-0043-109031. DOI

Boscia F., de Rosa V., Cammarota M., Secondo A., Pannaccione A., Annunziato L. The Na+/Ca2+ exchangers in demyelinating diseases. Cell Calcium. 2020;85 doi: 10.1016/j.ceca.2019.102130. PubMed DOI

Martino G., Grohovaz F., Brambilla E., Codazzi F., Consiglio A., Clementi E., Filippi M., Comi G., Grimaldi L.M. Proinflammatory cytokines regulate antigen-independent T-cell Activation by two separate calcium-signaling pathways in multiple sclerosis patients. Ann. Neurol. 1998;43:340–349. doi: 10.1002/ana.410430312. PubMed DOI

Asadikaram G., Meimand H.A.E., Noroozi S., Sanjari M., Zainodini N., Arababadi M.K. The effect of IFN-β 1a on expression of MDA5 and RIG-1 in multiple sclerosis patients. Biotechnol. Appl. Biochem. 2021;68:267–271. doi: 10.1002/bab.1920. PubMed DOI

Fischer J.C., Bscheider M., Eisenkolb G., Lin C.C., Wintges A., Otten V., Lindemans C.A., Heidegger S., Rudelius M., Monette S., et al. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury. Sci. Transl. Med. 2017;9 doi: 10.1126/scitranslmed.aag2513. PubMed DOI PMC

Thirion F., Sellebjerg F., Fan Y., Lyu L., Hansen T.H., Pons N., Levenez F., Quinquis B., Stankevic E., Søndergaard H.B., et al. The gut microbiota in multiple sclerosis varies with disease activity. Genome Med. 2023;15:1. doi: 10.1186/s13073-022-01148-1. PubMed DOI PMC

Sasa N., Kojima S., Koide R., Hasegawa T., Namkoong H., Hirota T., Watanabe R., Nakamura Y., Oguro-Igashira E., Ogawa K., et al. Blood DNA virome associates with autoimmune diseases and COVID-19. Nat. Genet. 2025;57:65–79. doi: 10.1038/s41588-024-02022-z. PubMed DOI PMC

Thijssen M., Devos T., Meyfroidt G., Van Ranst M., Pourkarim M.R. Exploring the relationship between anellovirus load and clinical variables in hospitalized COVID-19 patients: Implications for immune activation and inflammation. IJID Reg. 2023;9:49–54. doi: 10.1016/j.ijregi.2023.09.005. PubMed DOI PMC

Alseth E.O., Custodio R., Sundius S.A., Kuske R.A., Brown S.P., Westra E.R. The impact of phage and phage resistance on microbial community dynamics. PLoS Biol. 2024;22 doi: 10.1371/journal.pbio.3002346. PubMed DOI PMC

Godsil M., Ritz N.L., Venkatesh S., Meeske A.J. Gut phages and their interactions with bacterial and mammalian hosts. J. Bacteriol. 2025;207 doi: 10.1128/jb.00428-24. PubMed DOI PMC

Babcock G.J., Hochberg D., Thorley-Lawson A.D. The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity. 2000;13:497–506. doi: 10.1016/s1074-7613(00)00049-2. PubMed DOI

Beckers L., Baeten P., Popescu V., Swinnen D., Cardilli A., Hamad I., Van Wijmeersch B., Tavernier S.J., Kleinewietfeld M., Broux B., et al. Alterations in the innate and adaptive immune system in a real-world cohort of multiple sclerosis patients treated with ocrelizumab. Clin. Immunol. 2024;259 doi: 10.1016/j.clim.2024.109894. PubMed DOI

Sterling K.G., Dodd G.K., Alhamdi S., Asimenios P.G., Dagda R.K., De Meirleir K.L., Hudig D., Lombardi V.C. Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease. Int. J. Mol. Sci. 2022;23 PubMed PMC

Quesada-Simó A., Garrido-Marín A., Nos P., Gil-Perotín S. Impact of Anti-CD20 therapies on the immune homeostasis of gastrointestinal mucosa and their relationship with de novo intestinal bowel disease in multiple sclerosis: a review. Front. Pharmacol. 2023;14 doi: 10.3389/fphar.2023.1186016. PubMed DOI PMC

Le Gallou S., Zhou Z., Thai L.H., Fritzen R., de Los Aires A.V., Mégret J., Yu P., Kitamura D., Bille E., Tros F., et al. A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses. J. Exp. Med. 2018;215:2035–2053. doi: 10.1084/jem.20180977. PubMed DOI PMC

Sabatino J.J., Jr., Zamvil S.S., Hauser S.L. B-Cell Therapies in Multiple Sclerosis. Cold Spring Harb. Perspect. Med. 2019;9 doi: 10.1101/cshperspect.a032037. PubMed DOI PMC

Capasso N., Palladino R., Cerbone V., Spiezia A.L., Covelli B., Fiore A., Lanzillo R., Carotenuto A., Petracca M., Stanziola L., et al. Ocrelizumab effect on humoral and cellular immunity in multiple sclerosis and its clinical correlates: a 3-year observational study. J. Neurol. 2023;270:272–282. doi: 10.1007/s00415-022-11350-1. PubMed DOI PMC

Saidha S., Bell J., Harold S., Belisario J.M., Hawe E., Shao Q., Wyse K., Maiese E.M. Systematic literature review of immunoglobulin trends for anti-CD20 monoclonal antibodies in multiple sclerosis. Neurol. Sci. 2023;44:1515–1532. doi: 10.1007/s10072-022-06582-y. PubMed DOI PMC

Muñoz U., Sebal C., Escudero E., Esiri M., Tzartos J., Sloan C., Sadaba M.C. Main role of antibodies in demyelination and axonal damage in multiple sclerosis. Cell. Mol. Neurobiol. 2022;42:1809–1827. PubMed PMC

Baker D., Jacobs B.M., Gnanapavan S., Schmierer K., Giovannoni G. Plasma cell and B cell-targeted treatments for use in advanced multiple sclerosis. Mult. Scler. Relat. Disord. 2019;35:19–25. PubMed

Sokol H., Pigneur B., Watterlot L., Lakhdari O., Bermúdez-Humarán L.G., Gratadoux J.-J., Blugeon S., Bridonneau C., Furet J.-P., Corthier G. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl. Acad. Sci. USA. 2008;105:16731–16736. doi: 10.1073/pnas.0804812105. PubMed DOI PMC

Quevrain E., Maubert M.A., Michon C., Chain F., Marquant R., Tailhades J., Miquel S., Carlier L., Bermudez-Humaran L.G., Pigneur B., et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease. Gut. 2016;65:415–425. doi: 10.1136/gutjnl-2014-307649. PubMed DOI PMC

Rossi O., Khan M.T., Schwarzer M., Hudcovic T., Srutkova D., Duncan S.H., Stolte E.H., Kozakova H., Flint H.J., Samsom J.N., et al. Faecalibacterium prausnitzii strain HTF-F and its extracellular polymeric matrix attenuate clinical parameters in DSS-induced colitis. PLoS One. 2015;10 PubMed PMC

Teixeira B., Bittencourt V.C.B., Ferreira T.B., Kasahara T.M., Barros P.O., Alvarenga R., Hygino J., Andrade R.M., Andrade A.F., Bento C.A.M. Low sensitivity to glucocorticoid inhibition of in vitro Th17-related cytokine production in multiple sclerosis patients is related to elevated plasma lipopolysaccharide levels. Clin. Immunol. 2013;148:209–218. doi: 10.1016/j.clim.2013.05.012. PubMed DOI

Escribano B.M., Medina-Fernández F.J., Aguilar-Luque M., Agüera E., Feijoo M., Garcia-Maceira F.I., Lillo R., Vieyra-Reyes P., Giraldo A.I., Luque E., et al. Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model. Neurotherapeutics. 2017;14:199–211. doi: 10.1007/s13311-016-0480-0. PubMed DOI PMC

Lutterotti A., Kuenz B., Gredler V., Khalil M., Ehling R., Gneiss C., Egg R., Deisenhammer F., Berger T., Reindl M. Increased serum levels of soluble CD14 indicate stable multiple sclerosis. J. Neuroimmunol. 2006;181:145–149. doi: 10.1016/j.jneuroim.2006.09.002. PubMed DOI

Banks W.A., Gray A.M., Erickson M.A., Salameh T.S., Damodarasamy M., Sheibani N., Meabon J.S., Wing E.E., Morofuji Y., Cook D.G., Reed M.J. Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit. Neuroinflammation. 2015;12:223. doi: 10.1186/s12974-015-0434-1. PubMed DOI PMC

Lehikoinen J., Strandin T., Parantainen J., Nurmi K., Eklund K.K., Rivera F.J., Vaheri A., Tienari P.J. Fibrinolysis associated proteins and lipopolysaccharide bioactivity in plasma and cerebrospinal fluid in multiple sclerosis. J. Neuroimmunol. 2024;395 doi: 10.1016/j.jneuroim.2024.578432. PubMed DOI

Havrdova E., Arnold D.L., Bar-Or A., Comi G., Hartung H.P., Kappos L., Lublin F., Selmaj K., Traboulsee A., Belachew S., et al. No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a. Mult. Scler. J. Exp. Transl. Clin. 2018;4 doi: 10.1177/2055217318760642. PubMed DOI PMC

Thompson A.J., Banwell B.L., Barkhof F., Carroll W.M., Coetzee T., Comi G., Correale J., Fazekas F., Filippi M., Freedman M.S., et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162–173. doi: 10.1016/S1474-4422(17)30470-2. PubMed DOI

Schierova D., Roubalova R., Kolar M., Stehlikova Z., Rob F., Jackova Z., Coufal S., Thon T., Mihula M., Modrak M., et al. Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy. Cells. 2021;10 doi: 10.3390/cells10113188. PubMed DOI PMC

Coufal S., Galanova N., Bajer L., Gajdarova Z., Schierova D., Jiraskova Zakostelska Z., Kostovcikova K., Jackova Z., Stehlikova Z., Drastich P., et al. Inflammatory Bowel Disease Types Differ in Markers of Inflammation, Gut Barrier and in Specific Anti-Bacterial Response. Cells. 2019;8 doi: 10.3390/cells8070719. PubMed DOI PMC

Kadleckova D., Salakova M., Erban T., Tachezy R. Discovery and characterization of novel DNA viruses in Apis mellifera: expanding the honey bee virome through metagenomic analysis. mSystems. 2024;9 doi: 10.1128/msystems.00088-24. PubMed DOI PMC

Kadleckova D., Tachezy R., Erban T., Deboutte W., Nunvar J., Salakova M., Matthijnssens J. The Virome of Healthy Honey Bee Colonies: Ubiquitous Occurrence of Known and New Viruses in Bee Populations. mSystems. 2022;7 doi: 10.1128/msystems.00072-22. PubMed DOI PMC

Jiang H., Lei R., Ding S.W., Zhu S. Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads. BMC Bioinf. 2014;15:182. doi: 10.1186/1471-2105-15-182. PubMed DOI PMC

Callahan B.J., McMurdie P.J., Rosen M.J., Han A.W., Johnson A.J.A., Holmes S.P. DADA2: High-resolution sample inference from Illumina amplicon data. Methods. 2016;13:581–583. doi: 10.1038/nmeth.3869. PubMed DOI PMC

Edgar R.C., Haas B.J., Clemente J.C., Quince C., Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27:2194–2200. doi: 10.1093/bioinformatics/btr381. PubMed DOI PMC

Quast C., Pruesse E., Yilmaz P., Gerken J., Schweer T., Yarza P., Peplies J., Glöckner F.O. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41:D590–D596. doi: 10.1093/nar/gks1219. PubMed DOI PMC

McMurdie P.J., Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013;8 doi: 10.1371/journal.pone.0061217. PubMed DOI PMC

Jaccard P. Distribution de la Flore Alpine dans le Bassin des Dranses et dans quelques régions voisines. Bull. Soc. Vaud. Sci. Nat. 1901;37:241–272. doi: 10.5169/seals-266440. DOI

Bray J.R., Curtis J.T. An Ordination of the Upland Forest Communities of Southern Wisconsin. Ecol. Monogr. 1957;27:325–349.

Oksanen J., Blanchet F.G., Kindt R., Legendre P., Minchin P., O'Hara B., Simpson G., Solymos P., Stevens H., Wagner H. Vegan: Community Ecology Package. R Package Version 2.2-1. 2015;2:1–2.

Barnett D., Arts I., Penders J. microViz: an R package for microbiome data visualization and statistics. J. Open Source Softw. 2021;6:3201. doi: 10.21105/joss.03201. DOI

Mallick H., Rahnavard A., McIver L.J., Ma S., Zhang Y., Nguyen L.H., Tickle T.L., Weingart G., Ren B., Schwager E.H., et al. Multivariable association discovery in population-scale meta-omics studies. PLoS Comput. Biol. 2021;17 doi: 10.1371/journal.pcbi.1009442. PubMed DOI PMC

Douglas G.M., Maffei V.J., Zaneveld J.R., Yurgel S.N., Brown J.R., Taylor C.M., Huttenhower C., Langille M.G.I. PICRUSt2 for prediction of metagenome functions. Nat. Biotechnol. 2020;38:685–688. doi: 10.1038/s41587-020-0548-6. PubMed DOI PMC

Yang C., Mai J., Cao X., Burberry A., Cominelli F., Zhang L. ggpicrust2: an R package for PICRUSt2 predicted functional profile analysis and visualization. Bioinformatics. 2023;39 doi: 10.1093/bioinformatics/btad470. PubMed DOI PMC

Wickham H. Springer International Publishing; 2016. ggplot2: Elegant Graphics for Data Analysis.

Bolger A.M., Lohse M., Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–2120. doi: 10.1093/bioinformatics/btu170. PubMed DOI PMC

Nurk S., Meleshko D., Korobeynikov A., Pevzner P.A. metaSPAdes: a new versatile metagenomic assembler. Genome Res. 2017;27:824–834. doi: 10.1101/gr.213959.116. PubMed DOI PMC

Buchfink B., Xie C., Huson D.H. Fast and sensitive protein alignment using DIAMOND. Methods. 2015;12:59–60. doi: 10.1038/nmeth.3176. PubMed DOI

Ondov B.D., Bergman N.H., Phillippy A.M. Interactive metagenomic visualization in a Web browser. BMC Bioinf. 2011;12:385. doi: 10.1186/1471-2105-12-385. PubMed DOI PMC

Vasimuddin M.,M.S., Li H., Aluru S. 2019 IEEE International Parallel and Distributed Processing Symposium (IPDPS) 2019. Efficient Architecture-Aware Acceleration of BWA-MEM for Multicore Systems; pp. 314–324. DOI

Lahti L., Shetty S. microbiome R package. Bioconductor. DOI

Kolde R. pheatmap: Pretty Heatmaps. https://github.com/raivokolde/pheatmap R package version.

Kassambara A. ggpubr: ‘ggplot2’ Based Publication Ready Plots. https://cran.r-project.org/web/packages/ggpubr/index.html

Szklarczyk D., Kirsch R., Koutrouli M., Nastou K., Mehryary F., Hachilif R., Gable A.L., Fang T., Doncheva N.T., Pyysalo S., et al. The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51:D638–D646. doi: 10.1093/nar/gkac1000. PubMed DOI PMC

R Core Team . R Foundation for Statistical Computing; Vienna, Austria: 2020. R: A Language and Environment for Statistical Computing.http://www.r-project.org/index.html