Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications

Author(s): Xu Wang, Zhen Liang, Shengnan Wang, Di Ma, Mingqin Zhu* and Jiachun Feng*

Volume 20, Issue 7, 2022

Published on: 30 March, 2022

Page: [1413 - 1426] Pages: 14

DOI: 10.2174/1570159X19666210629145351

Price: $65

Open Access Journals Promotions 2
Abstract

The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota have also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.

Keywords: Gut microbiota, multiple sclerosis, neuro-inflammatory diseases, gut-microbiota-brain axis, blood-brain barrier, fecal microbiota transplantation, antibiotic treatment, probiotic microbiota.

Graphical Abstract
[1]
Structure, function and diversity of the healthy human microbiome. Nature 2012; 486(7402): 207-14.
[http://dx.doi.org/10.1038/nature11234] [PMID: 22699609]
[2]
Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature 2007; 449(7164): 804-10.
[http://dx.doi.org/10.1038/nature06244] [PMID: 17943116]
[3]
Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006; 124(4): 837-48.
[http://dx.doi.org/10.1016/j.cell.2006.02.017] [PMID: 16497592]
[4]
Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464(7285): 59-65.
[http://dx.doi.org/10.1038/nature08821] [PMID: 20203603]
[5]
Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe 2015; 17(5): 565-76.
[http://dx.doi.org/10.1016/j.chom.2015.04.011] [PMID: 25974299]
[6]
Bauer KC, Huus KE, Finlay BB. Microbes and the mind: emerging hallmarks of the gut microbiota-brain axis. Cell Microbiol 2016; 18(5): 632-44.
[http://dx.doi.org/10.1111/cmi.12585] [PMID: 26918908]
[7]
Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science 2001; 292(5519): 1115-8.
[http://dx.doi.org/10.1126/science.1058709] [PMID: 11352068]
[8]
Mosca A, Leclerc M, Hugot JP. Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosys-tem? Front Microbiol 2016; 7: 455.
[http://dx.doi.org/10.3389/fmicb.2016.00455] [PMID: 27065999]
[9]
Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? revisiting the ratio of bacterial to host cells in humans. Cell 2016; 164(3): 337-40.
[http://dx.doi.org/10.1016/j.cell.2016.01.013] [PMID: 26824647]
[10]
Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflammation 2019; 16(1): 53.
[http://dx.doi.org/10.1186/s12974-019-1434-3] [PMID: 30823925]
[11]
Larroya-García A, Navas-Carrillo D, Orenes-Piñero E. Impact of gut microbiota on neurological diseases: Diet composition and novel treatments. Crit Rev Food Sci Nutr 2019; 59(19): 3102-16.
[http://dx.doi.org/10.1080/10408398.2018.1484340] [PMID: 29870270]
[12]
Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 2014; 146(6): 1489-99.
[http://dx.doi.org/10.1053/j.gastro.2014.02.009] [PMID: 24560869]
[13]
Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490(7418): 55-60.
[http://dx.doi.org/10.1038/nature11450] [PMID: 23023125]
[14]
Arrieta MC, Stiemsma LT, Dimitriu PA, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med 2015; 7(307): 307ra152.
[http://dx.doi.org/10.1126/scitranslmed.aab2271] [PMID: 26424567]
[15]
Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457(7228): 480-4.
[http://dx.doi.org/10.1038/nature07540] [PMID: 19043404]
[16]
Dinan TG, Cryan JF. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. 2017; 595(2): 489-503.
[http://dx.doi.org/10.1113/JP273106]
[17]
Lassmann H, Bradl M. Multiple sclerosis: experimental models and reality. Acta Neuropathol 2017; 133(2): 223-44.
[http://dx.doi.org/10.1007/s00401-016-1631-4] [PMID: 27766432]
[18]
Magyari M, Sorensen PS. The changing course of multiple sclerosis: rising incidence, change in geographic distribution, disease course, and prognosis. Curr Opin Neurol 2019; 32(3): 320-6.
[http://dx.doi.org/10.1097/WCO.0000000000000695] [PMID: 30925518]
[19]
Orton SM, Herrera BM, Yee IM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 2006; 5(11): 932-6.
[http://dx.doi.org/10.1016/S1474-4422(06)70581-6] [PMID: 17052660]
[20]
Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83(3): 278-86.
[http://dx.doi.org/10.1212/WNL.0000000000000560] [PMID: 24871874]
[21]
Garg N, Smith TW. An update on immunopathogenesis, diagnosis, and treatment of multiple sclerosis. Brain Behav 2015; 5(9): e00362.
[http://dx.doi.org/10.1002/brb3.362] [PMID: 26445701]
[22]
Correale J, Gaitán MI, Ysrraelit MC, Fiol MP. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain 2017; 140(3): 527-46.
[PMID: 27794524]
[23]
Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol 2019; 26(1): 27-40.
[http://dx.doi.org/10.1111/ene.13819] [PMID: 30300457]
[24]
Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med 2006; 354(9): 942-55.
[http://dx.doi.org/10.1056/NEJMra052130] [PMID: 16510748]
[25]
McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 2007; 8(9): 913-9.
[http://dx.doi.org/10.1038/ni1507] [PMID: 17712344]
[26]
Prat A, Antel J. Pathogenesis of multiple sclerosis. Curr Opin Neurol 2005; 18(3): 225-30.
[http://dx.doi.org/10.1097/01.wco.0000169737.99040.31] [PMID: 15891404]
[27]
Sadovnick AD, Armstrong H, Rice GP, et al. A population-based study of multiple sclerosis in twins: update. Ann Neurol 1993; 33(3): 281-5.
[http://dx.doi.org/10.1002/ana.410330309] [PMID: 8498811]
[28]
Mumford CJ, Wood NW, Kellar-Wood H, Thorpe JW, Miller DH, Compston DA. The British Isles survey of multiple sclerosis in twins. Neurology 1994; 44(1): 11-5.
[http://dx.doi.org/10.1212/WNL.44.1.11] [PMID: 8290043]
[29]
Alfredsson L, Olsson T. Lifestyle and Environmental Factors in Multiple Sclerosis. Cold Spring Harb Perspect Med 2019; 9(4): a028944.
[http://dx.doi.org/10.1101/cshperspect.a028944] [PMID: 29735578]
[30]
Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabo-lism in mice. Science 2013; 341(6150): 1241214.
[http://dx.doi.org/10.1126/science.1241214] [PMID: 24009397]
[31]
Cantarel BL, Waubant E, Chehoud C, et al. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med 2015; 63(5): 729-34.
[http://dx.doi.org/10.1097/JIM.0000000000000192] [PMID: 25775034]
[32]
Miyake S, Kim S, Suda W, et al. 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 2015; 10(9): e0137429.
[http://dx.doi.org/10.1371/journal.pone.0137429] [PMID: 26367776]
[33]
Tremlett H, Fadrosh DW, Faruqi AA, et al. Gut microbiota composition and re-lapse risk in pediatric MS: A pilot study. J Neurol Sci 2016; 363: 153-7.
[http://dx.doi.org/10.1016/j.jns.2016.02.042] [PMID: 27000242]
[34]
Jangi S, Gandhi R, Cox LM, Li N, von Glehn F. Alterations of the human gut microbiome in multiple sclerosis. 2016; 7: 12015.
[http://dx.doi.org/10.1038/ncomms12015]
[35]
Berer K, Mues M, Koutrolos M, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 2011; 479(7374): 538-41.
[http://dx.doi.org/10.1038/nature10554] [PMID: 22031325]
[36]
Budhram A, Parvathy S, Kremenchutzky M, Silverman M. Breaking down the gut microbiome composition in multiple sclerosis. Mult Scler 2017; 23(5): 628-36.
[http://dx.doi.org/10.1177/1352458516682105] [PMID: 27956557]
[37]
Mirza A, Forbes JD, Zhu F, et al. The multiple sclerosis gut microbiota: A systematic review. Mult Scler Relat Disord 2020; 37: 101427.
[http://dx.doi.org/10.1016/j.msard.2019.101427] [PMID: 32172998]
[38]
Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The central nervous system and the gut microbiome. Cell 2016; 167(4): 915-32.
[http://dx.doi.org/10.1016/j.cell.2016.10.027] [PMID: 27814521]
[39]
Durgan DJ, Lee J, McCullough LD, Bryan RM Jr. Examining the role of the microbiota-gut-brain axis in stroke. Stroke 2019; 50(8): 2270-7.
[http://dx.doi.org/10.1161/STROKEAHA.119.025140] [PMID: 31272315]
[40]
Burokas A, Moloney RD, Dinan TG, Cryan JF. Microbiota regulation of the mammalian gut-brain axis. Adv Appl Microbiol 2015; 91: 1-62.
[http://dx.doi.org/10.1016/bs.aambs.2015.02.001] [PMID: 25911232]
[41]
Martin CR, Osadchiy V, Kalani A, Mayer EA. The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol 2018; 6(2): 133-48.
[http://dx.doi.org/10.1016/j.jcmgh.2018.04.003] [PMID: 30023410]
[42]
Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011; 12(8): 453-66.
[http://dx.doi.org/10.1038/nrn3071] [PMID: 21750565]
[43]
Strader AD, Woods SC. Gastrointestinal hormones and food intake. Gastroenterology 2005; 128(1): 175-91.
[http://dx.doi.org/10.1053/j.gastro.2004.10.043] [PMID: 15633135]
[44]
Wang FB, Powley TL. Vagal innervation of intestines: afferent pathways mapped with new en bloc horseradish peroxidase adaptation. Cell Tissue Res 2007; 329(2): 221-30.
[http://dx.doi.org/10.1007/s00441-007-0413-7] [PMID: 17453246]
[45]
Asano Y, Hiramoto T, Nishino R, et al. Critical role of gut microbiota in the pro-duction of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol 2012; 303(11): G1288-95.
[http://dx.doi.org/10.1152/ajpgi.00341.2012] [PMID: 23064760]
[46]
Barrett E. Ross, R.P.; O’Toole, P.W.; Fitzgerald, G.F.; Stanton, C. γ-aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 2012; 113(2): 411-7.
[http://dx.doi.org/10.1111/j.1365-2672.2012.05344.x] [PMID: 22612585]
[47]
Erny D. Hrabě de Angelis, A.L.; Jaitin, D.; Wieghofer, P.; Staszewski, O.; David, E.; Keren-Shaul, H.; Mahlakoiv, T.; Jakobshagen, K.; Buch, T.; Schwierzeck, V.; Utermöhlen, O.; Chun, E.; Garrett, W.S.; McCoy, K.D.; Diefenbach, A.; Staeheli, P.; Stecher, B.; Amit, I.; Prinz, M. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 2015; 18(7): 965-77.
[http://dx.doi.org/10.1038/nn.4030] [PMID: 26030851]
[48]
Sun J, Ling Z, Wang F, et al. Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis. Neurosci Lett 2016; 613: 30-5.
[http://dx.doi.org/10.1016/j.neulet.2015.12.047] [PMID: 26733300]
[49]
Sun J, Wang F, Ling Z, et al. Clostridium butyricum attenuates cerebral ischemia/reperfusion injury in diabetic mice via modulation of gut microbiota. Brain Res 2016; 1642: 180-8.
[http://dx.doi.org/10.1016/j.brainres.2016.03.042] [PMID: 27037183]
[50]
Singh V, Roth S, Llovera G, et al. Microbiota dysbiosis controls the neuroin-flammatory response after stroke. J Neurosci 2016; 36(28): 7428-40.
[http://dx.doi.org/10.1523/JNEUROSCI.1114-16.2016] [PMID: 27413153]
[51]
Benakis C, Brea D, Caballero S, et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med 2016; 22(5): 516-23.
[http://dx.doi.org/10.1038/nm.4068] [PMID: 27019327]
[52]
Ochoa-Repáraz J, Mielcarz DW, Ditrio LE, et al. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol 2009; 183(10): 6041-50.
[http://dx.doi.org/10.4049/jimmunol.0900747] [PMID: 19841183]
[53]
Gevers D, Kugathasan S, Denson LA, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 2014; 15(3): 382-92.
[http://dx.doi.org/10.1016/j.chom.2014.02.005] [PMID: 24629344]
[54]
Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease pa-tients. Proc Natl Acad Sci USA 2008; 105(43): 16731-6.
[http://dx.doi.org/10.1073/pnas.0804812105] [PMID: 18936492]
[55]
Scher JU, Sczesnak A, Longman RS, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2013; 2: e01202.
[http://dx.doi.org/10.7554/eLife.01202] [PMID: 24192039]
[56]
Nusrat S, Gulick E, Levinthal D, Bielefeldt K. Anorectal dysfunction in multiple sclerosis: a systematic review. ISRN Neurol 2012; 2012: 376023.
[http://dx.doi.org/10.5402/2012/376023] [PMID: 22900202]
[57]
Minuk GY, Lewkonia RM. Possible familial association of multiple sclerosis and inflammatory bowel disease. N Engl J Med 1986; 314(9): 586.
[http://dx.doi.org/10.1056/NEJM198602273140921] [PMID: 3945303]
[58]
Sadovnick AD, Paty DW, Yannakoulias G. Concurrence of multiple sclerosis and inflammatory bowel disease. N Engl J Med 1989; 321(11): 762-3.
[http://dx.doi.org/10.1056/NEJM198909143211115] [PMID: 2770807]
[59]
Yacyshyn B, Meddings J, Sadowski D, Bowen-Yacyshyn MB. Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Dig Dis Sci 1996; 41(12): 2493-8.
[http://dx.doi.org/10.1007/BF02100148] [PMID: 9011463]
[60]
Kimura K, Hunter SF, Thollander MS, et al. Concurrence of inflammatory bowel disease and multiple sclerosis. Mayo Clin Proc 2000; 75(8): 802-6.
[http://dx.doi.org/10.4065/75.8.802] [PMID: 10943233]
[61]
Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating diseases in patients with inflammatory bowel disease. Gastroenterology 2005; 129(3): 819-26.
[http://dx.doi.org/10.1053/j.gastro.2005.06.022] [PMID: 16143121]
[62]
Ott SJ, Musfeldt M, Wenderoth DF, et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 2004; 53(5): 685-93.
[http://dx.doi.org/10.1136/gut.2003.025403] [PMID: 15082587]
[63]
Manichanh C, Rigottier-Gois L, Bonnaud E, et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 2006; 55(2): 205-11.
[http://dx.doi.org/10.1136/gut.2005.073817] [PMID: 16188921]
[64]
Chen J, Chia N, Kalari KR, et al. Multiple sclerosis patients have a distinct gut mi-crobiota compared to healthy controls. Sci Rep 2016; 6: 28484.
[http://dx.doi.org/10.1038/srep28484] [PMID: 27346372]
[65]
Castillo-Álvarez F, Pérez-Matute P, Oteo JA, Marzo-Sola ME. The influence of interferon β-1b on gut microbiota composition in patients with multiple sclerosis. Neurologia (Engl Ed) 2018; S0213-4853(18)30158-0.
[PMID: 29895466]
[66]
Tremlett H, Fadrosh DW, Faruqi AA, et al. Gut microbiota in early pediat-ric multiple sclerosis: a case-control study. Eur J Neurol 2016; 23(8): 1308-21.
[http://dx.doi.org/10.1111/ene.13026] [PMID: 27176462]
[67]
Cosorich I, Dalla-Costa G, Sorini C, et al. High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis. Sci Adv 2017; 3(7): e1700492-.
[http://dx.doi.org/10.1126/sciadv.1700492] [PMID: 28706993]
[68]
Goverman J, Woods A, Larson L, Weiner LP, Hood L, Zaller DM. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 1993; 72(4): 551-60.
[http://dx.doi.org/10.1016/0092-8674(93)90074-Z] [PMID: 7679952]
[69]
Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental auto-immune encephalomyelitis. Proc Natl Acad Sci USA 2011; 108(Suppl. 1): 4615-22.
[http://dx.doi.org/10.1073/pnas.1000082107] [PMID: 20660719]
[70]
Ochoa-Repáraz J, Mielcarz DW, Ditrio LE, et al. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J Immunol 2010; 185(7): 4101-8.
[http://dx.doi.org/10.4049/jimmunol.1001443] [PMID: 20817872]
[71]
Mangalam A, Shahi SK, Luckey D, et al. Human gut-derived commensal bacteria suppress CNS inflammatory and demyelinating disease. Cell Rep 2017; 20(6): 1269-77.
[http://dx.doi.org/10.1016/j.celrep.2017.07.031] [PMID: 28793252]
[72]
Lavasani S, Dzhambazov B, Nouri M, et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One 2010; 5(2): e9009.
[http://dx.doi.org/10.1371/journal.pone.0009009] [PMID: 20126401]
[73]
Berer K, Gerdes LA, Cekanaviciute E, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci USA 2017; 114(40): 10719-24.
[http://dx.doi.org/10.1073/pnas.1711233114] [PMID: 28893994]
[74]
Cekanaviciute E, Yoo BB, Runia TF. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. 2017; 114(40): 10713-10718.
[http://dx.doi.org/10.1073/pnas.1711235114]
[75]
Buscarinu MC, Cerasoli B, Annibali V, et al. Altered intestinal permeability in patients with re-lapsing-remitting multiple sclerosis: A pilot study. Mult Scler 2017; 23(3): 442-6.
[http://dx.doi.org/10.1177/1352458516652498] [PMID: 27270497]
[76]
Buscarinu MC, Romano S, Mechelli R, et al. Intestinal permeability in relapsing-remitting multiple sclerosis. Neurotherapeutics 2018; 15(1): 68-74.
[http://dx.doi.org/10.1007/s13311-017-0582-3] [PMID: 29119385]
[77]
Nouri M, Bredberg A, Weström B, Lavasani S. Intestinal barrier dysfunction develops at the onset of experimental autoimmune en-cephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS One 2014; 9(9): e106335.
[http://dx.doi.org/10.1371/journal.pone.0106335] [PMID: 25184418]
[78]
Welcome MO. Gut microbiota disorder, gut epithelial and blood-brain barrier dysfunctions in etiopathogenesis of dementia: molecular mechanisms and signaling pathways. Neuromolecular Med 2019; 21(3): 205-26.
[http://dx.doi.org/10.1007/s12017-019-08547-5] [PMID: 31115795]
[79]
Obermeier B, Mentele R, Malotka J, et al. Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis. Nat Med 2008; 14(6): 688-93.
[http://dx.doi.org/10.1038/nm1714] [PMID: 18488038]
[80]
Tintoré M, Rovira A, Brieva L, et al. Isolated demyelinating syndromes: comparison of CSF oligoclonal bands and different MR imaging criteria to predict conversion to CDMS. Mult Scler 2001; 7(6): 359-63.
[http://dx.doi.org/10.1177/135245850100700603] [PMID: 11795456]
[81]
Cameron EM, Spencer S, Lazarini J, et al. Potential of a unique antibody gene signature to predict conversion to clinically definite multiple sclerosis. J Neuroimmunol 2009; 213(1-2): 123-30.
[http://dx.doi.org/10.1016/j.jneuroim.2009.05.014] [PMID: 19631394]
[82]
O’Connor KC, Appel H, Bregoli L, et al. Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. J Immunol 2005; 175(3): 1974-82.
[http://dx.doi.org/10.4049/jimmunol.175.3.1974] [PMID: 16034142]
[83]
Yan W, Nguyen T, Yuki N, et al. Antibodies to neurofascin exacerbate adoptive transfer experimental autoimmune neuritis. J Neuroimmunol 2014; 277(1-2): 13-7.
[http://dx.doi.org/10.1016/j.jneuroim.2014.09.012] [PMID: 25262157]
[84]
Derfuss T, Parikh K, Velhin S, et al. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci USA 2009; 106(20): 8302-7.
[http://dx.doi.org/10.1073/pnas.0901496106] [PMID: 19416878]
[85]
Srivastava R, Aslam M, Kalluri SR, et al. Potassium channel KIR4.1 as an immune target in multiple sclerosis. N Engl J Med 2012; 367(2): 115-23.
[http://dx.doi.org/10.1056/NEJMoa1110740] [PMID: 22784115]
[86]
Kinzel S, Lehmann-Horn K, Torke S, et al. Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen. Acta Neuropathol 2016; 132(1): 43-58.
[http://dx.doi.org/10.1007/s00401-016-1559-8] [PMID: 27022743]
[87]
Wekerle H. Brain autoimmunity and intestinal microbiota: 100 trillion game changers. Trends Immunol 2017; 38(7): 483-97.
[http://dx.doi.org/10.1016/j.it.2017.03.008] [PMID: 28601415]
[88]
Lebeer S, Vanderleyden J, De Keersmaecker SC. Host interactions of probiotic bacterial surface molecules: comparison with commen-sals and pathogens. Nat Rev Microbiol 2010; 8(3): 171-84.
[http://dx.doi.org/10.1038/nrmicro2297] [PMID: 20157338]
[89]
Cusick MF, Libbey JE, Fujinami RS. Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allergy Immunol 2012; 42(1): 102-11.
[http://dx.doi.org/10.1007/s12016-011-8294-7] [PMID: 22095454]
[90]
Rojas M, Restrepo-Jiménez P, Monsalve DM, et al. Molecular mimicry and autoimmunity. J Autoimmun 2018; 95: 100-23.
[http://dx.doi.org/10.1016/j.jaut.2018.10.012] [PMID: 30509385]
[91]
Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: a new clinical frontier. Gut 2016; 65(2): 330-9.
[http://dx.doi.org/10.1136/gutjnl-2015-309990] [PMID: 26338727]
[92]
Hebbandi Nanjundappa R, Ronchi F, Wang J, et al. Bas-solas-Molina, H.; Salas, A.; Khan, H.; Slattery, R.M.; Wyss, M.; Mooser, C.; Macpherson, A.J.; Sycuro, L.K.; Serra, P.; McKay, D.M.; McCoy, K.D.; Santamaria, P. A gut microbial mimic that hijacks diabetogenic autoreactivity to suppress colitis. Cell 2017; 171(3): 655-667.e17.
[http://dx.doi.org/10.1016/j.cell.2017.09.022] [PMID: 29053971]
[93]
Anderson B, Park BJ, Verdaguer J, Amrani A, Santamaria P. Prevalent CD8(+) T cell response against one peptide/MHC complex in autoimmune diabetes. Proc Natl Acad Sci USA 1999; 96(16): 9311-6.
[http://dx.doi.org/10.1073/pnas.96.16.9311] [PMID: 10430939]
[94]
Lieberman SM, Evans AM, Han B, et al. Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proc Natl Acad Sci USA 2003; 100(14): 8384-8.
[http://dx.doi.org/10.1073/pnas.0932778100] [PMID: 12815107]
[95]
Varrin-Doyer M, Spencer CM, Schulze-Topphoff U, et al. Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Ann Neurol 2012; 72(1): 53-64.
[http://dx.doi.org/10.1002/ana.23651] [PMID: 22807325]
[96]
Martin R, Gran B, Zhao Y, et al. Molecular mimicry and antigen-specific T cell responses in multiple sclerosis and chronic CNS Lyme disease. J Autoimmun 2001; 16(3): 187-92.
[http://dx.doi.org/10.1006/jaut.2000.0501] [PMID: 11334482]
[97]
Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995; 80(5): 695-705.
[http://dx.doi.org/10.1016/0092-8674(95)90348-8] [PMID: 7534214]
[98]
Markovic-Plese S, Hemmer B, Zhao Y, Simon R, Pinilla C, Martin R. High level of cross-reactivity in influenza virus hemaggluti-nin-specific CD4+ T-cell response: implications for the initiation of autoimmune response in multiple sclerosis. J Neuroimmunol 2005; 169(1-2): 31-8.
[http://dx.doi.org/10.1016/j.jneuroim.2005.07.014] [PMID: 16150497]
[99]
Schrijver IA, van Meurs M, Melief MJ, et al. Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis. Brain 2001; 124(Pt 8): 1544-54.
[http://dx.doi.org/10.1093/brain/124.8.1544] [PMID: 11459746]
[100]
Hughes LE, Smith PA, Bonell S, et al. Cross-reactivity between related sequences found in Acinetobacter sp., Pseudomonas aeruginosa, myelin basic protein and myelin oligodendro-cyte glycoprotein in multiple sclerosis. J Neuroimmunol 2003; 144(1-2): 105-15.
[http://dx.doi.org/10.1016/S0165-5728(03)00274-1] [PMID: 14597104]
[101]
Planas R, Santos R, Tomas-Ojer P. GDP-l-fucose synthase is a CD4(+) T cell-specific autoantigen in DRB3*02:02 patients with multi-ple sclerosis. Sci Transl Med 2018; 10(462): eaat4301.
[http://dx.doi.org/10.1126/scitranslmed.aat4301] [PMID: 30305453]
[102]
Gloor SM, Wachtel M, Bolliger MF, Ishihara H, Landmann R, Frei K. Molecular and cellular permeability control at the blood-brain barrier. Brain Res Brain Res Rev 2001; 36(2-3): 258-64.
[http://dx.doi.org/10.1016/S0165-0173(01)00102-3] [PMID: 11690623]
[103]
Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta 2011; 1812(2): 252-64.
[http://dx.doi.org/10.1016/j.bbadis.2010.06.017] [PMID: 20619340]
[104]
Erdő F.; Denes, L.; de Lange, E. Age-associated physiological and pathological changes at the blood-brain barrier: A review. J Cereb Blood Flow Metab 2017; 37(1): 4-24.
[http://dx.doi.org/10.1177/0271678X16679420] [PMID: 27837191]
[105]
Wang X, Jiao W, Lin M, et al. Resolution of inflammation in neuromyelitis optica spectrum disorders. Mult Scler Relat Disord 2019; 27: 34-41.
[http://dx.doi.org/10.1016/j.msard.2018.09.040] [PMID: 30300851]
[106]
Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008; 57(2): 178-201.
[http://dx.doi.org/10.1016/j.neuron.2008.01.003] [PMID: 18215617]
[107]
Agrawal SM, Yong VW. Immunopathogenesis of multiple sclerosis. Int Rev Neurobiol 2007; 79: 99-126.
[http://dx.doi.org/10.1016/S0074-7742(07)79005-0] [PMID: 17531839]
[108]
Michel L, Prat A. One more role for the gut: microbiota and blood brain barrier. Ann Transl Med 2016; 4(1): 15.
[PMID: 26855951]
[109]
Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med 2014; 6(263): 263ra158.
[http://dx.doi.org/10.1126/scitranslmed.3009759] [PMID: 25411471]
[110]
Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 2001; 81(3): 1031-64.
[http://dx.doi.org/10.1152/physrev.2001.81.3.1031] [PMID: 11427691]
[111]
Braniste V, Al-Asmakh M, Kowal C. The gut microbiota influences blood-brain barrier permeability in mice Sci Transl Med 2014; 6(263): 263ra158-263ra158.
[http://dx.doi.org/10.1126/scitranslmed.3009759]
[112]
Boveri M, Kinsner A, Berezowski V, et al. Highly purified lipoteichoic acid from gram-positive bacteria induces in vitro blood-brain barrier disruption through glia activation: role of pro-inflammatory cytokines and nitric oxide. Neuroscience 2006; 137(4): 1193-209.
[http://dx.doi.org/10.1016/j.neuroscience.2005.10.011] [PMID: 16343789]
[113]
Banks WA, Gray AM, Erickson MA, et al. Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroin-flammation, and elements of the neurovascular unit. J Neuroinflammation 2015; 12: 223-3.
[http://dx.doi.org/10.1186/s12974-015-0434-1] [PMID: 26608623]
[114]
Nicol B, Salou M, Laplaud D-A, Wekerle H. The autoimmune concept of multiple sclerosis. Presse Med 2015; 44(4 Pt 2): e103-12.
[http://dx.doi.org/10.1016/j.lpm.2015.02.009] [PMID: 25813101]
[115]
Lassmann H. Multiple sclerosis pathology: evolution of pathogenetic concepts. Brain Pathol 2005; 15(3): 217-22.
[http://dx.doi.org/10.1111/j.1750-3639.2005.tb00523.x] [PMID: 16196388]
[116]
Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implica-tions for the pathogenesis of demyelination. Ann Neurol 2000; 47(6): 707-17.
[http://dx.doi.org/10.1002/1531-8249(200006)47:6<707:AID-ANA3>3.0.CO;2-Q] [PMID: 10852536]
[117]
Dutta R, Trapp BD. Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology 2007; 68(22)(Suppl. 3): S22-31.
[http://dx.doi.org/10.1212/01.wnl.0000275229.13012.32] [PMID: 17548565]
[118]
Lassmann H, Brück W, Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 2001; 7(3): 115-21.
[http://dx.doi.org/10.1016/S1471-4914(00)01909-2] [PMID: 11286782]
[119]
Brucklacher-Waldert V, Stuerner K, Kolster M, Wolthausen J, Tolosa E. Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 2009; 132(Pt 12): 3329-41.
[http://dx.doi.org/10.1093/brain/awp289] [PMID: 19933767]
[120]
Matusevicius D, Kivisäkk P, He B, et al. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler 1999; 5(2): 101-4.
[http://dx.doi.org/10.1177/135245859900500206] [PMID: 10335518]
[121]
Durelli L, Conti L, Clerico M, et al. T-helper 17 cells expand in mul-tiple sclerosis and are inhibited by interferon-beta. Ann Neurol 2009; 65(5): 499-509.
[http://dx.doi.org/10.1002/ana.21652] [PMID: 19475668]
[122]
Tzartos JS, Friese MA, Craner MJ, et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008; 172(1): 146-55.
[http://dx.doi.org/10.2353/ajpath.2008.070690] [PMID: 18156204]
[123]
Stockinger B, Veldhoen M, Martin B. Th17 T cells: linking innate and adaptive immunity. Semin Immunol 2007; 19(6): 353-61.
[http://dx.doi.org/10.1016/j.smim.2007.10.008] [PMID: 18023589]
[124]
Atarashi K, Tanoue T, Oshima K, et al. Treg in-duction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013; 500(7461): 232-6.
[http://dx.doi.org/10.1038/nature12331] [PMID: 23842501]
[125]
Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature 2016; 535(7610): 75-84.
[http://dx.doi.org/10.1038/nature18848] [PMID: 27383982]
[126]
Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010; 107(27): 12204-9.
[http://dx.doi.org/10.1073/pnas.0909122107] [PMID: 20566854]
[127]
Ochoa-Repáraz J, Mielcarz DW, Wang Y, et al. A polysaccharide from the hu-man commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol 2010; 3(5): 487-95.
[http://dx.doi.org/10.1038/mi.2010.29] [PMID: 20531465]
[128]
Ooijevaar RE, Terveer EM, Verspaget HW, Kuijper EJ, Keller JJ. Clinical application and potential of fecal microbiota transplanta-tion. Annu Rev Med 2019; 70: 335-51.
[http://dx.doi.org/10.1146/annurev-med-111717-122956] [PMID: 30403550]
[129]
Borody T, Leis S, Campbell J, Torres M, Nowak A. Fecal microbiota transplantation (FMT) in multiple sclerosis (MS): 942. Am J Gastroenterol 2011; 106: S352.
[http://dx.doi.org/10.14309/00000434-201110002-00942]
[130]
Makkawi S, Camara-Lemarroy C, Metz L. Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS. Neurol Neuroimmunol Neuroinflam 2018; 5(4): e459.
[http://dx.doi.org/10.1212/NXI.0000000000000459]
[131]
Schepici G, Silvestro S, Bramanti P, Mazzon E. The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials. Cell Transplant 2019; 28(12): 1507-27.
[http://dx.doi.org/10.1177/0963689719873890] [PMID: 31512505]
[132]
Shahi SK, Freedman SN, Mangalam AK. Gut microbiome in multiple sclerosis: The players involved and the roles they play. Gut Microbes 2017; 8(6): 607-15.
[http://dx.doi.org/10.1080/19490976.2017.1349041] [PMID: 28696139]
[133]
Goodrich JK, Waters JL, Poole AC, et al. Human genetics shape the gut microbiome. Cell 2014; 159(4): 789-99.
[http://dx.doi.org/10.1016/j.cell.2014.09.053] [PMID: 25417156]
[134]
Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 2013; 339(6123): 1084-8.
[http://dx.doi.org/10.1126/science.1233521] [PMID: 23328391]
[135]
Hollister EB, Riehle K, Luna RA, et al. Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome 2015; 3: 36.
[http://dx.doi.org/10.1186/s40168-015-0101-x] [PMID: 26306392]
[136]
Biedermann L, Zeitz J, Mwinyi J, et al. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PLoS One 2013; 8(3): e59260.
[http://dx.doi.org/10.1371/journal.pone.0059260] [PMID: 23516617]
[137]
Norman JM, Handley SA, Baldridge MT, et al. Dis-ease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 2015; 160(3): 447-60.
[http://dx.doi.org/10.1016/j.cell.2015.01.002] [PMID: 25619688]
[138]
Kernbauer E, Ding Y, Cadwell K. An enteric virus can replace the beneficial function of commensal bacteria. Nature 2014; 516(7529): 94-8.
[http://dx.doi.org/10.1038/nature13960] [PMID: 25409145]
[139]
Davenport ER, Mizrahi-Man O, Michelini K, Barreiro LB, Ober C, Gilad Y. Seasonal variation in human gut microbiome compo-sition. PLoS One 2014; 9(3): e90731.
[http://dx.doi.org/10.1371/journal.pone.0090731] [PMID: 24618913]
[140]
David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505(7484): 559-63.
[http://dx.doi.org/10.1038/nature12820] [PMID: 24336217]
[141]
Le Chatelier E, Nielsen T, Qin J, et al. Richness of hu-man gut microbiome correlates with metabolic markers. Nature 2013; 500(7464): 541-6.
[http://dx.doi.org/10.1038/nature12506] [PMID: 23985870]
[142]
Piccio L, Stark JL, Cross AH. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J Leukoc Biol 2008; 84(4): 940-8.
[http://dx.doi.org/10.1189/jlb.0208133] [PMID: 18678605]
[143]
Kleinewietfeld M, Manzel A, Titze J, et al. Sodium chloride drives autoim-mune disease by the induction of pathogenic TH17 cells. Nature 2013; 496(7446): 518-22.
[http://dx.doi.org/10.1038/nature11868] [PMID: 23467095]
[144]
Munger KL, Bentzen J, Laursen B, et al. Childhood body mass index and multiple sclerosis risk: a long-term cohort study. Mult Scler 2013; 19(10): 1323-9.
[http://dx.doi.org/10.1177/1352458513483889] [PMID: 23549432]
[145]
Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolat-ed syndrome. Neurology 2013; 80(6): 548-52.
[http://dx.doi.org/10.1212/WNL.0b013e31828154f3] [PMID: 23365063]
[146]
Esposito S, Bonavita S, Sparaco M, Gallo A, Tedeschi G. The role of diet in multiple sclerosis: A review. Nutr Neurosci 2018; 21(6): 377-90.
[http://dx.doi.org/10.1080/1028415X.2017.1303016] [PMID: 28338444]
[147]
Schirmer M, Smeekens SP, Vlamakis H, et al. Linking the human gut microbiome to inflammatory cytokine production capacity. Cell 2016; 167(4): 1125-1136.e8.
[http://dx.doi.org/10.1016/j.cell.2016.10.020] [PMID: 27814509]
[148]
Crost EH, Tailford LE, Le Gall G, Fons M, Henrissat B, Juge N. Utilisation of mucin glycans by the human gut symbiont Rumino-coccus gnavus is strain-dependent. PLoS One 2013; 8(10): e76341.
[http://dx.doi.org/10.1371/journal.pone.0076341] [PMID: 24204617]
[149]
Shahi SK, Jensen SN, Murra AC, et al. Human Commensal Prevotella histicola Ameliorates Disease as Effectively as Interferon-Beta in the Experimental Autoimmune Encepha-lomyelitis. Front Immunol 2020; 11: 578648.
[http://dx.doi.org/10.3389/fimmu.2020.578648] [PMID: 33362764]
[150]
Shahi SK, Freedman SN, Murra AC, et al. Prevotella histicola, a human gut commensal, is as potent as COPAXONE® in an animal model of multiple sclerosis. Front Immunol 2019; 10: 462.
[http://dx.doi.org/10.3389/fimmu.2019.00462] [PMID: 30984162]
[151]
Sivieri K, Morales ML, Adorno MA, Sakamoto IK, Saad SM, Rossi EA. Lactobacillus acidophilus CRL 1014 improved “gut health” in the SHIME reactor. BMC Gastroenterol 2013; 13: 100.
[http://dx.doi.org/10.1186/1471-230X-13-100] [PMID: 23758634]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy