{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:03:46Z","timestamp":1785528226681,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder, characterized by progressive demyelination and neuronal cell loss in the central nervous system. Many possible causes of MS have been proposed, including genetic factors, environmental triggers, and infectious agents. Recently, Clostridium perfringens epsilon toxin (ETX) has been incriminated in MS, based initially on the isolation of the bacteria from a MS patient, combined with an immunoreactivity to ETX. To investigate a putative causative role of ETX in MS, we analyzed the pattern of antibodies reacting to the toxin using a sensitive qualitative assay. This prospective observational study included one hundred patients with relapsing remitting multiple sclerosis (RRMS), all untreated, and ninety matched healthy controls. By assessing the isotypic pattern and serum concentration of ETX-reacting antibodies, our study shows a predominant IgM response over IgG and IgA antibody responses both in MS patients and controls, and significantly higher levels of IgM reacting to ETX in MS patients compared to the control group. A longitudinal follow-up of ETX-specific antibody response in a subgroup of MS patients did not show any correlation with disease evolution. Overall, these unexpected findings are not compatible with a specific recognition of ETX by serum antibodies from MS patients. They rather argue for a cross immunological reactivity with an antigen, possibly an autoantigen, mimicking ETX. Thus, our data argue against the hypothesis of a causal relationship between C. perfringens ETX and MS.<\/jats:p>","DOI":"10.3390\/toxins17010027","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T03:38:41Z","timestamp":1736221121000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Does Clostridium Perfringens Epsilon Toxin Mimic an Auto-Antigen Involved in Multiple Sclerosis?"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7531-7713","authenticated-orcid":false,"given":"Marie-Lise","family":"Gougeon","sequence":"first","affiliation":[{"name":"Unit\u00e9 Immunit\u00e9 Inn\u00e9e et Virus, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris, Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Seffer","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Immunit\u00e9 Inn\u00e9e et Virus, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris, Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezarela","family":"Hoxha","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des Toxines Bact\u00e9riennes, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR 2001 INSERM U1306, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7699-0328","authenticated-orcid":false,"given":"Elisabeth","family":"Maillart","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Neurologie, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Multiple Sclerosis Center, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9305-8989","authenticated-orcid":false,"given":"Michel R.","family":"Popoff","sequence":"additional","affiliation":[{"name":"Unit\u00e9 des Toxines Bact\u00e9riennes, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR 2001 INSERM U1306, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e37297","DOI":"10.1097\/MD.0000000000037297","article-title":"Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment","volume":"103","author":"Haki","year":"2024","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and Treatment of Multiple Sclerosis: A Review","volume":"325","author":"McGinley","year":"2021","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/WCO.0000000000000572","article-title":"MRI in multiple sclerosis: What is changing?","volume":"31","author":"Filippi","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S1474-4422(22)00289-7","article-title":"Multiple sclerosis progression: Time for a new mechanism-driven framework","volume":"22","author":"Kuhlmann","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nrneurol.2016.59","article-title":"Advanced MRI and staging of multiple sclerosis lesions","volume":"12","author":"Absinta","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Grunwald, C., Kretowska-Grunwald, A., Adamska-Patruno, E., Kochanowicz, J., Kulakowska, A., and Chorazy, M. (2024). The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis-A Systematic Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052589"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neuroscience.2024.04.004","article-title":"Immune System Dysregulation in the Progression of Multiple Sclerosis: Molecular Insights and Therapeutic Implications","volume":"548","author":"Khan","year":"2024","journal-title":"Neuroscience"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Riedhammer, C., and Weissert, R. (2015). Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00322"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e20190460","DOI":"10.1084\/jem.20190460","article-title":"Pathogenic T cell cytokines in multiple sclerosis","volume":"217","author":"Wagner","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Christovich, A., and Luo, X.M. (2022). Gut Microbiota, Leaky Gut, and Autoimmune Diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.946248"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hoffman, K., Doyle, W.J., Schumacher, S.M., and Ochoa-Reparaz, J. (2023). Gut microbiome-modulated dietary strategies in EAE and multiple sclerosis. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1146748"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tian, H., Huang, D., Wang, J., Li, H., Gao, J., Zhong, Y., Xia, L., Zhang, A., Lin, Z., and Ke, X. (2024). The role of the \u201cgut microbiota-mitochondria\u201d crosstalk in the pathogenesis of multiple sclerosis. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1404995"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2250229","DOI":"10.1002\/eji.202250229","article-title":"Microbiota, diet, and the gut-brain axis in multiple sclerosis and stroke","volume":"53","author":"Kantsjo","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"ref_15","first-page":"505","article-title":"Rubella virus might increase risk of MS","volume":"20","author":"Kiani","year":"2024","journal-title":"Nat. Rev. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rumah, K.R., Linden, J., Fischetti, V.A., and Vartanian, T. (2013). Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076359"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1177\/1352458518767327","article-title":"Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis","volume":"25","author":"Wagley","year":"2019","journal-title":"Mult. Scler. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e163239","DOI":"10.1172\/JCI163239","article-title":"Epsilon toxin-producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege","volume":"133","author":"Ma","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1111\/j.1742-4658.2011.08145.x","article-title":"Epsilon toxin: A fascinating pore-forming toxin","volume":"278","author":"Popoff","year":"2011","journal-title":"FEBS J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.anaerobe.2018.04.011","article-title":"Expansion of the Clostridium perfringens toxin-based typing scheme","volume":"53","author":"Rood","year":"2018","journal-title":"Anaerobe"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Titball, R.W. (2024). The Molecular Architecture and Mode of Action of Clostridium perfringens epsilon-Toxin. Toxins, 16.","DOI":"10.3390\/toxins16040180"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1177\/104063870802000526","article-title":"Ulcerative enterocolitis in two goats associated with enterotoxin- and beta2 toxin-positive Clostridium perfringens type D","volume":"20","author":"Uzal","year":"2008","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.anaerobe.2018.06.002","article-title":"Comparative pathogenesis of enteric clostridial infections in humans and animals","volume":"53","author":"Uzal","year":"2018","journal-title":"Anaerobe"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lonchamp, E., Dupont, J.L., Wioland, L., Courjaret, R., Mbebi-Liegeois, C., Jover, E., Doussau, F., Popoff, M.R., Bossu, J.L., and de Barry, J. (2010). Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013046"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.toxicon.2007.04.025","article-title":"Distribution of Clostridium perfringens epsilon toxin in the brains of acutely intoxicated mice and its effect upon glial cells","volume":"50","author":"Dorca","year":"2007","journal-title":"Toxicon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/cmi.12373","article-title":"Epsilon toxin from Clostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination","volume":"17","author":"Wioland","year":"2015","journal-title":"Cell. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Finnie, J.W., and Uzal, F.A. (2022). Pathology and Pathogenesis of Brain Lesions Produced by Clostridium perfringens Type D Epsilon Toxin. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169050"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Linden, J.R., Ma, Y., Zhao, B., Harris, J.M., Rumah, K.R., Schaeren-Wiemers, N., and Vartanian, T. (2015). Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination. mBio, 6.","DOI":"10.1128\/mBio.02513-14"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rumah, K.R., Ma, Y., Linden, J.R., Oo, M.L., Anrather, J., Schaeren-Wiemers, N., Alonso, M.A., Fischetti, V.A., McClain, M.S., and Vartanian, T. (2015). The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens epsilon-Toxin. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004896"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"00086-18","DOI":"10.1128\/MCB.00086-18","article-title":"The Cytotoxicity of Epsilon Toxin from Clostridium perfringens on Lymphocytes Is Mediated by MAL Protein Expression","volume":"38","author":"Blanch","year":"2018","journal-title":"Mol. Cell. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1177\/13524585231186899","article-title":"Is Clostridium perfringens epsilon toxin associated with multiple sclerosis?","volume":"29","author":"Titball","year":"2023","journal-title":"Mult. Scler. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0140-6736(55)91276-9","article-title":"Recovery of Clostridium welchii type D from man","volume":"268","author":"Kohn","year":"1955","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41541-019-0128-2","article-title":"Clostridium perfringens epsilon toxin vaccine candidate lacking toxicity to cells expressing myelin and lymphocyte protein","volume":"4","author":"Morcrette","year":"2019","journal-title":"NPJ Vaccines"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6125","DOI":"10.1016\/j.vaccine.2010.07.046","article-title":"Potency against enterotoxemia of a recombinant Clostridium perfringens type D epsilon toxoid in ruminants","volume":"28","author":"Lobato","year":"2010","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Moreira, G.M., Salvarani, F.M., da Cunha, C.E., Mendonca, M., Moreira, A.N., Goncalves, L.A., Pires, P.S., Lobato, F.C., and Conceicao, F.R. (2016). Immunogenicity of a Trivalent Recombinant Vaccine Against Clostridium perfringens Alpha, Beta, and Epsilon Toxins in Farm Ruminants. Sci. Rep., 6.","DOI":"10.1038\/srep22816"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Huss, A., Bachhuber, F., Feraudet-Tarisse, C., Hiergeist, A., and Tumani, H. (2024). Multiple Sclerosis and Clostridium perfringens Epsilon Toxin: Is There a Relationship?. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071392"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41582-022-00700-2","article-title":"Pathogenic autoantibodies in multiple sclerosis\u2014From a simple idea to a complex concept","volume":"18","author":"Hoftberger","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/135245859800400304","article-title":"The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis","volume":"4","author":"Reiber","year":"1998","journal-title":"Mult. Scler. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1212\/01.WNL.0000070782.27949.F7","article-title":"Chlamydia pneumoniae in children with MS: Frequency and quantity of intrathecal antibodies","volume":"61","author":"Rostasy","year":"2003","journal-title":"Neurology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7864","DOI":"10.1073\/pnas.1522730113","article-title":"Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins","volume":"113","author":"Brandle","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1172\/JCI22833","article-title":"Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS","volume":"115","author":"Villar","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Munoz, U., Sebal, C., Escudero, E., Urcelay, E., Arroyo, R., Garcia-Martinez, M.A., Quintana, F.J., Alvarez-Lafuente, R., and Sadaba, M.C. (2022). Serum levels of IgM to phosphatidylcholine predict the response of multiple sclerosis patients to natalizumab or IFN-beta. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-16218-y"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17562864231189919","DOI":"10.1177\/17562864231189919","article-title":"IgM to phosphatidylcholine in multiple sclerosis patients: From the diagnosis to the treatment","volume":"16","author":"Escudero","year":"2023","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jaut.2013.01.006","article-title":"Natural autoantibodies in the physiology and pathophysiology of the immune system","volume":"41","author":"Avrameas","year":"2013","journal-title":"J. Autoimmun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1172\/JCI29943","article-title":"Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics","volume":"117","author":"Merbl","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nagele, E.P., Han, M., Acharya, N.K., DeMarshall, C., Kosciuk, M.C., and Nagele, R.G. (2013). Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060726"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1007\/s10875-014-0025-4","article-title":"Natural IgM: Beneficial autoantibodies for the control of inflammatory and autoimmune disease","volume":"34","author":"Gronwall","year":"2014","journal-title":"J. Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4049\/jimmunol.1400844","article-title":"Natural antibodies bridge innate and adaptive immunity","volume":"194","author":"Panda","year":"2015","journal-title":"J. Immunol."},{"key":"ref_49","first-page":"384","article-title":"Clostridium welchii epsilon toxin in the intestinal contents of man","volume":"268","author":"Bullen","year":"1955","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e169643","DOI":"10.1172\/JCI169643","article-title":"Clostridium epsilon toxin is excessive in multiple sclerosis and provokes multifocal lesions in mouse models","volume":"133","author":"Reder","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.vetmic.2008.02.015","article-title":"Binding of epsilon-toxin from Clostridium perfringens in the nervous system","volume":"131","author":"Gibert","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Linden, J.R., Flores, C., Schmidt, E.F., Uzal, F.A., Michel, A.O., Valenzuela, M., Dobrow, S., and Vartanian, T. (2019). Clostridium perfringens epsilon toxin induces blood brain barrier permeability via caveolae-dependent transcytosis and requires expression of MAL. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1008014"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1023\/A:1006362819202","article-title":"Resistance of ovine, caprine and bovine endothelial cells to Clostridium perfringens type D epsilon toxin in vitro","volume":"23","author":"Uzal","year":"1999","journal-title":"Vet. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Goldstein, J., Morris, W.E., Loidl, C.F., Tironi-Farinati, C., McClane, B.A., Uzal, F.A., and Fernandez Miyakawa, M.E. (2009). Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007065"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Shetty, S.V., Mazzucco, M.R., Winokur, P., Haigh, S.V., Rumah, K.R., Fischetti, V.A., Vartanian, T., and Linden, J.R. (2023). Clostridium perfringens Epsilon Toxin Binds to and Kills Primary Human Lymphocytes. Toxins, 15.","DOI":"10.3390\/toxins15070423"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ouyang, Q., Yu, H., Xu, L., Yu, M., and Zhang, Y. (2024). Relationship between gut microbiota and multiple sclerosis: A scientometric visual analysis from 2010 to 2023. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1451742"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Torres-Chavez, M.E., Torres-Carrillo, N.M., Monreal-Lugo, A.V., Garnes-Rancurello, S., Murugesan, S., Gutierrez-Hurtado, I.A., Beltran-Ramirez, J.R., Sandoval-Pinto, E., and Torres-Carrillo, N. (2023). Association of intestinal dysbiosis with susceptibility to multiple sclerosis: Evidence from different population studies (Review). Biomed. Rep., 19.","DOI":"10.3892\/br.2023.1675"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.4103\/1673-5374.387974","article-title":"Gut flora in multiple sclerosis: Implications for pathogenesis and treatment","volume":"19","author":"Zhang","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Dunalska, A., Saramak, K., and Szejko, N. (2023). The Role of Gut Microbiome in the Pathogenesis of Multiple Sclerosis and Related Disorders. Cells, 12.","DOI":"10.3390\/cells12131760"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Chang, S.H., and Choi, Y. (2023). Gut dysbiosis in autoimmune diseases: Association with mortality. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1157918"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nsmb804","article-title":"Clostridium perfringens epsilon-toxin shows structural similarity to the pore-forming toxin aerolysin","volume":"11","author":"Cole","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.vaccine.2008.12.021","article-title":"Safety and immunogenicity of SC599, an oral live attenuated Shigella dysenteriae type-1 vaccine in healthy volunteers: Results of a Phase 2, randomized, double-blind placebo-controlled trial","volume":"27","author":"Launay","year":"2009","journal-title":"Vaccine"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/1\/27\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:23:59Z","timestamp":1759919039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/1\/27"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["toxins17010027"],"URL":"https:\/\/doi.org\/10.3390\/toxins17010027","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]}}}