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The gut microbiota and associated metabolites in multiple sclerosis

Yunshu Wang1 ,  Zihao Li2 ,  Yun Xu2 ,  Cun-Jin Zhang1,2*
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1 Department of Basic Research, Medical School of Nanjing University, Nanjing, Jiangsu, China
2 Department of Neurology, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu, China
Advanced Neurology 2023, 2(3), 413 https://doi.org/10.36922/an.413
Submitted: 30 March 2023 | Accepted: 10 July 2023 | Published: 26 July 2023
© 2023 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Multiple sclerosis (MS) is a severe central nervous system autoimmune inflammatory disease featured by the presence of infiltrated immune cells, demyelination, and degeneration. Recent research has shown that gut microbiota, including some commensal bacteria, is capable of interacting with the host immune system and remarkably influencing the development and outcome of experimental autoimmune encephalomyelitis, a classic animal model of MS. In addition, gut dysbiosis, presented with a significantly altered composition of commensal bacteria, is linked to the immune response and inflammation, such as Th17 activation and B cell function. Moreover, it has been observed that microbiota impacts the immune system by regulating the metabolites in the gut. In this review, we summarize the new research on the relationship and mechanism between the gut microbiota and MS, as well as the implications for developing new strategies in MS by modulating the gut microbiota and metabolites.

Keywords
Gut
Microbiota
Metabolites
Multiple sclerosis
Inflammation
Funding
National Natural Science Fund for Excellent Young Scholars
Nanjing special fund for Medical Science and Technology Development Projects for Distinguished Young Scholars
National Natural Science Foundation of China
The Fundamental Research Funds for the Central Universities the Key Research
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Dendrou CA, Fugger L, Friese MA, 2015, Immunopathology of multiple sclerosis. Nat Rev Immunol, 15: 545–558. https://doi.org/10.1038/nri3871

 

  1. Fox EJ, 2004, Immunopathology of multiple sclerosis. Neurology 63: S3–S7. https://doi.org/10.1212/wnl.63.12_suppl_6.s3

 

  1. Harbo HF, Gold R, Tintore M, 2013, Sex and gender issues in multiple sclerosis. Ther Adv Neurol Disord, 6: 237–248. https://doi.org/10.1177/1756285613488434

 

  1. Sospedra M, Martin R, 2005, Immunology of multiple sclerosis. Annu Rev Immunol, 23: 683–747. https://doi.org/10.1146/annurev.immunol.23.021704.115707

 

  1. Bar-Or A, Li R, 2021, Cellular immunology of relapsing multiple sclerosis: Interactions, checks, and balances. Lancet Neurol, 20: 470–483. https://doi.org/10.1016/S1474-4422(21)00063-6

 

  1. Fletcher JM, Lalor SJ, Sweeney CM, et al., 2010, T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol, 162: 1–11. https://doi.org/10.1111/j.1365-2249.2010.04143.x

 

  1. Cekanaviciute E, Yoo BB, Runia TF, et al., 2017, Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A, 114: 10713–10718. https://doi.org/10.1073/pnas.1711235114

 

  1. Cantarel BL, Waubant E, Chehoud C, et al., 2015, Gut microbiota in multiple sclerosis: Possible influence of immunomodulators. J Investig Med, 63: 729–734. https://doi.org/10.1097/JIM.0000000000000192

 

  1. Tremlett H, Zhu F, Arnold D, et al., 2021, The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes. Ann Clin Transl Neurol, 8: 2252–2269. https://doi.org/10.1002/acn3.51476

 

  1. Cosorich I, Dalla-Costa G, Sorini C, et al., 2017, High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis. Sci Adv, 3: e1700492. https://doi.org/10.1126/sciadv.1700492

 

  1. Miyake S, Kim S, Suda W, et al., 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: e0137429. https://doi.org/10.1371/journal.pone.0137429

 

  1. Zeng Q, Gong J, Liu X, et al, 2019, Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis. Neurochem Int, 129: 104468. https://doi.org/10.1016/j.neuint.2019.104468

 

  1. Tremlett H, Fadrosh DW, Faruqi AA, et al., 2016, Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. BMC Neurol, 16: 182. https://doi.org/10.1186/s12883-016-0703-3

 

  1. Kadowaki A, Saga R, Lin Y, et al., 2019, Gut microbiota-dependent CCR9+CD4+ T cells are altered in secondary progressive multiple sclerosis. Brain, 142: 916–931. https://doi.org/10.1093/brain/awz012

 

  1. Scher JU, Ubeda C, Artacho A, et al., 2015, Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol, 67: 128–139. https://doi.org/10.1002/art.38892

 

  1. Steri M, Orrù V, Idda ML, et al., 2017, Overexpression of the cytokine BAFF and autoimmunity risk. N Engl J Med, 376: 1615–1626. https://doi.org/10.1056/NEJMoa1610528

 

  1. Hauser SL, Waubant E, Arnold DL, et al., 2008, B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med, 358: 676–688. https://doi.org/10.1056/NEJMoa0706383

 

  1. Rojas OL, Pröbstel AK, Porfilio EA, et al., 2019, Recirculating intestinal iga-producing cells regulate neuroinflammation via IL-10. Cell, 177: 492–493. https://doi.org/10.1016/j.cell.2019.03.037

 

  1. Ivanov II, Atarashi K, Manel N, et al., 2009, Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 139: 485–498. https://doi.org/10.1016/j.cell.2009.09.033

 

  1. Lee YK, Menezes JS, Umesaki Y, et al., 2011, Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A, 108 Suppl 1: 4615–4622. https://doi.org/10.1073/pnas.1000082107

 

  1. Berer K, Mues M, Koutrolos M, et al., 2011, Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature, 479: 538–541. https://doi.org/10.1038/nature10554

 

  1. Yang Y, Torchinsky MB, Gobert M, et al., 2014, Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature, 510: 152–156. https://doi.org/10.1038/nature13279

 

  1. Sano T, Huang W, Hall JA, et al., 2015, An IL-23R/IL-22 Circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell, 163: 381–393. https://doi.org/10.1016/j.cell.2015.08.061

 

  1. Lai NY, Musser MA, Pinho-Ribeiro FA, et al., 2020, Gut-innervating nociceptor neurons regulate peyer’s patch microfold cells and SFB levels to mediate Salmonella host defense. Cell, 180: 33–49, e22. https://doi.org/10.1016/j.cell.2019.11.014

 

  1. Omura S, Sato F, Park AM, et al., 2020, Bioinformatics analysis of gut microbiota and CNS transcriptome in virus-Induced acute myelitis and chronic Inflammatory demyelination; potential association of distinct bacteria with CNS IgA upregulation. Front Immunol, 11: 1138. https://doi.org/10.3389/fimmu.2020.01138

 

  1. Stanisavljević S, Lukić J, Soković S, et al., 2016, Correlation of gut microbiota composition with resistance to experimental autoimmune encephalomyelitis in rats. Front Microbiol, 7: 2005. https://doi.org/10.3389/fmicb.2016.02005

 

  1. Lin X, Liu Y, Ma L, et al., 2021, Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice. J Transl Med, 19: 317. https://doi.org/10.1186/s12967-021-02995-z

 

  1. Derrien M, Vaughan EE, Plugge CM, et al., 2004, Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol, 54: 1469–1476. https://doi.org/10.1099/ijs.0.02873-0

 

  1. Derrien M, Van Baarlen P, Hooiveld G, et al., 2011, Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol, 2: 166. https://doi.org/10.3389/fmicb.2011.00166

 

  1. Ganesh BP, Klopfleisch R, Loh G, et al., 2013, Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice. PLoS One, 8: e74963. https://doi.org/10.1371/journal.pone.0074963

 

  1. Berer K, Gerdes LA, Cekanaviciute E, et al., 2017, Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A, 14: 10719–10724. https://doi.org/10.1073/pnas.1711233114

 

  1. Nunes PR, Romao-Veiga M, Matias ML, et al., 2022, Vitamin D decreases expression of NLRP1 and NLRP3 inflammasomes in placental explants from women with preeclampsia cultured with hydrogen peroxide. Hum Immunol, 83: 74–80. https://doi.org/10.1016/j.humimm.2021.10.002

 

  1. Jiang S, Zhang H, Li X, et al., 2021, Vitamin D/VDR attenuate cisplatin-induced AKI by down-regulating NLRP3/Caspase-1/GSDMD pyroptosis pathway. J Steroid Biochem Mol Biol, 206: 105789. https://doi.org/10.1016/j.jsbmb.2020.105789

 

  1. Donovan C, Liu G, Shen S, et al., 2020, The role of the microbiome and the NLRP3 inflammasome in the gut and lung. J Leukoc Biol, 108: 925–935. https://doi.org/10.1002/JLB.3MR0720-472RR

 

  1. Jangi S, Gandhi R, Cox LM, et al., 2016, Alterations of the human gut microbiome in multiple sclerosis. Nat Commun, 7: 12015. https://doi.org/10.1038/ncomms12015

 

  1. Cox LM, Maghzi AH, Liu S, et al., 2021, Gut microbiome in progressive multiple sclerosis. Ann Neurol, 89: 1195–1211. https://doi.org/10.1002/ana.26084

 

  1. Chen J, Chia N, Kalari KR, et al., 2016, Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep, 6: 28484. https://doi.org/10.1038/srep28484

 

  1. Korkina L, Kostyuk V, De Luca C, et al., 2011, Plant phenylpropanoids as emerging anti-inflammatory agents. Mini Rev Med Chem, 11: 823–835. https://doi.org/10.2174/138955711796575489

 

  1. Schogor AL, Huws SA, Santos GT, et al., 2014, Ruminal Prevotella spp. may play an important role in the conversion of plant lignans into human health beneficial antioxidants. PLoS One, 9: e87949. https://doi.org/10.1371/journal.pone.0087949

 

  1. Toh H, Oshima K, Suzuki T, et al., 2013, Complete genome sequence of the equol-producing bacterium Adlercreutzia equolifaciens DSM 19450T. Genome Announc, 1. https://doi.org/10.1128/genomeA.00742-13

 

  1. Saresella M, Marventano I, Barone M, et al., 2020, Alterations in circulating fatty acid are associated with gut microbiota dysbiosis and inflammation in multiple sclerosis. Front Immunol, 11: 1390. https://doi.org/10.3389/fimmu.2020.01390

 

  1. Barone M, Mendozzi L, D’Amico F, et al., 2021, Influence of a high-impact multidimensional rehabilitation program on the gut microbiota of patients with multiple sclerosis. Int J Mol Sci, 22: 7173. https://doi.org/10.3390/ijms22137173

 

  1. Mangalam A, Shahi SK, Luckey D, et al., 2017, Human gut-derived commensal bacteria suppress CNS inflammatory and demyelinating disease. Cell Rep, 20: 1269–1277. https://doi.org/10.1016/j.celrep.2017.07.031

 

  1. Horton MK, McCauley K, Fadrosh D, et al., 2021, Gut microbiome is associated with multiple sclerosis activity in children. Ann Clin Transl Neurol, 8: 1867–1883. https://doi.org/10.1002/acn3.51441

 

  1. Peng L, Li ZR, Green RS, et al., 2009, Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr, 139: 1619–1625. https://doi.org/10.3945/jn.109.104638

 

  1. Dalile B, Van Oudenhove L, Vervliet B, et al., 2019, The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol, 16: 461–478. https://doi.org/10.1038/s41575-019-0157-3

 

  1. Bachem A, Makhlouf C, Binger KJ, et al., 2019, Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T Cells. Immunity, 51: 285–297.e5. https://doi.org/10.1016/j.immuni.2019.06.002

 

  1. Mitchell RW, On NH, Del Bigio MR, et al., 2011, Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells. J Neurochem, 117: 735–746. https://doi.org/10.1111/j.1471-4159.2011.07245.x

 

  1. Bonini JA, Anderson SM, Steiner DF, 1997, Molecular cloning and tissue expression of a novel orphan G protein-coupled receptor from rat lung. Biochem Biophys Res Commun, 234: 190–193. https://doi.org/10.1006/bbrc.1997.6591

 

  1. Kim CH, 2018, Immune regulation by microbiome metabolites. Immunology, 154: 220–229. https://doi.org/10.1111/imm.12930

 

  1. Deleu S, Machiels K, Raes J, et al., 2021, Short chain fatty acids and its producing organisms: An overlooked therapy for IBD? EBioMedicine, 66: 103293. https://doi.org/10.1016/j.ebiom.2021.103293

 

  1. Park J, Wang Q, Wu Q, et al., 2019, Bidirectional regulatory potentials of short-chain fatty acids and their G-protein-coupled receptors in autoimmune neuroinflammation. Sci Rep, 9: 8837. https://doi.org/10.1038/s41598-019-45311-y

 

  1. Duscha A, Gisevius B, Hirschberg S, et al., 2020, Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism. Cell, 180: 1067–1080.e16. https://doi.org/10.1016/j.cell.2020.02.035

 

  1. Takewaki D, Suda W, Sato W, et al., 2020, Alterations of the gut ecological and functional microenvironment in different stages of multiple sclerosis. Proc Natl Acad Sci U S A, 117: 22402–22412. https://doi.org/10.1073/pnas.2011703117

 

  1. Ling Z, Cheng Y, Yan X, et al., 2020, Alterations of the fecal microbiota in Chinese patients with multiple sclerosis. Front Immunol, 11: 590783. https://doi.org/10.3389/fimmu.2020.590783

 

  1. Luu M, Pautz S, Kohl V, et al., 2019, The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes. Nat Commun, 10: 760. https://doi.org/10.1038/s41467-019-08711-2

 

  1. Haase S, Mäurer J, Duscha A, et al., 2021, Propionic acid rescues high-fat diet enhanced immunopathology in autoimmunity via effects on Th17 responses. Front Immunol, 12: 701626. https://doi.org/10.3389/fimmu.2021.701626

 

  1. Perez-Perez S, Domínguez-Mozo MI, Alonso-Gómez A, et al., 2020, Acetate correlates with disability and immune response in multiple sclerosis. PeerJ, 8: e10220. https://doi.org/10.7717/peerj.10220

 

  1. Olsson A, Gustavsen S, Nguyen TD, et al., 2021, Serum short-chain fatty acids and associations with inflammation in newly diagnosed patients with multiple sclerosis and healthy controls. Front Immunol, 12: 661493. https://doi.org/10.3389/fimmu.2021.661493

 

  1. Lim CK, Bilgin A, Lovejoy DB, et al., 2017, Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression. Sci Rep, 7: 41473. https://doi.org/4147310.1038/srep41473

 

  1. Rothhammer V, Mascanfroni ID, Bunse L, et al., 2016, Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med, 22: 586–597. https://doi.org/10.1038/nm.4106

 

  1. Nourbakhsh B, Bhargava P, Tremlett H, et al., 2018, Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course. Ann Clin Transl Neurol, 5: 1211–1221. https://doi.org/10.1002/acn3.637

 

  1. Rothhammer V, Borucki DM, Sanchez MI, et al., 2017, Dynamic regulation of serum aryl hydrocarbon receptor agonists in MS. Neurol Neuroimmunol Neuroinflamm, 4: e359. https://doi.org/10.1212/NXI.0000000000000359

 

  1. Kaye J, Piryatinsky V, Birnberg T, et al., 2016, Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A, 113: E6145–E6152. https://doi.org/10.1073/pnas.1607843113

 

  1. Rothhammer V, Kenison JE, Li Z, et al., 2021, Aryl hydrocarbon receptor activation in astrocytes by laquinimod ameliorates autoimmune inflammation in the CNS. Neurol Neuroimmunol Neuroinflamm, 8: e946. https://doi.org/10.1212/NXI.0000000000000946

 

  1. Vollmer TL, Sorensen PS, Selmaj K, et al., 2014, A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol, 261: 773–783. https://doi.org/10.1007/s00415-014-7264-4

 

  1. Wilck N, Matus MG, Kearney SM, et al., 2017, Salt-responsive gut commensal modulates TH17 axis and disease. Nature, 551: 585–589. https://doi.org/10.1038/nature24628

 

  1. Rothhammer V, Borucki DM, Tjon EC, et al., 2018, Microglial control of astrocytes in response to microbial metabolites. Nature, 557: 724–728. https://doi.org/10.1038/s41586-018-0119-x

 

  1. Rietjens IMC, Louisse J, Beekmann K, 2017, The potential health effects of dietary phytoestrogens. Br J Pharmacol, 174: 1263–1280. https://doi.org/10.1111/bph.13622

 

  1. Masilamani M, Wei J, Sampson HA, 2012, Regulation of the immune response by soybean isoflavones. Immunol Res, 54: 95–110. https://doi.org/10.1007/s12026-012-8331-5

 

  1. Rafii F, 2015, The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol. Metabolites, 5: 56–73. https://doi.org/10.3390/metabo5010056

 

  1. Clavel T, Borrmann D, Braune A, et al., 2006, Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe, 12: 140–147. https://doi.org/10.1016/j.anaerobe.2005.11.002

 

  1. Freedman SN, Shahi SK, Mangalam AK, 2018, The “gut feeling”: Breaking down the role of gut microbiome in multiple sclerosis. Neurotherapeutics, 15: 109–125. https://doi.org/10.1007/s13311-017-0588-x

 

  1. Jensen SN, Cady NM, Shahi SK, et al., 2021, Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis. Sci Adv, 7: eabd4595. https://doi.org/10.1126/sciadv.abd4595

 

  1. Suez J, Zmora N, Segal E, et al., 2019, The pros, cons, and many unknowns of probiotics. Nat Med, 25: 716–729. https://doi.org/10.1038/s41591-019-0439-x

 

  1. Morshedi M, Hashemi R, Moazzen S, et al., 2019, Immunomodulatory and anti-inflammatory effects of probiotics in multiple sclerosis: A systematic review. J Neuroinflammation, 16: 231. https://doi.org/10.1186/s12974-019-1611-4

 

  1. Mestre L, Carrillo-Salinas FJ, Feliú A, et al., 2020, How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing commensal bacteria into the neurodegenerative process. Gut Microbes, 12: 1813532. https://doi.org/10.1080/19490976.2020.1813532

 

  1. Calvo-Barreiro L, Eixarch H, Ponce-Alonso M, et al., 2020, A commercial probiotic induces tolerogenic and reduces pathogenic responses in experimental autoimmune encephalomyelitis. Cells, 9: 906. https://doi.org/10.3390/cells9040906

 

  1. Colpitts SL, Kasper EJ, Keever A, et al., 2017, A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis. Gut Microbes, 8: 561–573. https://doi.org/10.1080/19490976.2017.1353843

 

  1. Tankou SK, Regev K, Healy BC, et al., 2018. A probiotic modulates the microbiome and immunity in multiple sclerosis. Ann Neurol, 83: 1147–1161. https://doi.org/10.1002/ana.25244

 

  1. Abdurasulova IN, Matsulevich AV, Tarasova EA, et al., 2016, Enterococcus faecium strain L-3 and glatiramer acetate ameliorate experimental allergic encephalomyelitis in rats by affecting different populations of immune cells. Benef Microbes, 7: 719–729. https://doi.org/10.3920/BM2016.0018

 

  1. Secher T, Kassem S, Benamar M, et al., 2017, Oral administration of the probiotic strain Escherichia coli Nissle 1917 reduces susceptibility to neuroinflammation and repairs experimental autoimmune encephalomyelitis-induced intestinal barrier dysfunction. Front Immunol, 8: 1096. https://doi.org/10.3389/fimmu.2017.01096

 

  1. He B, Hoang TK, Tian X, et al., 2019, Lactobacillus reuteri reduces the severity of experimental autoimmune encephalomyelitis in mice by modulating gut microbiota. Front Immunol, 10: 385. https://doi.org/10.3389/fimmu.2019.00385

 

  1. Kouchaki E, Tamtaji OR, Salami M, et al., 2017, Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr, 36: 1245–1249. https://doi.org/10.1016/j.clnu.2016.08.015

 

  1. Tamtaji OR, Kouchaki E, Salami M, et al., 2017, The effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. J Am Coll Nutr, 36: 660–665. https://doi.org/10.1080/07315724.2017.1347074

 

  1. Miyauchi E, Kim SW, Suda W, et al., 2020, Gut microorganisms act together to exacerbate inflammation in spinal cords. Nature, 585: 102–106. https://doi.org/10.1038/s41586-020-2634-9

 

  1. Montgomery TL, Künstner A, Kennedy JJ, et al., 2020, Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity. Proc Natl Acad Sci U S A, 117: 27516–27527. https://doi.org/10.1073/pnas.2002817117

 

  1. Mestre L, Carrillo-Salinas FJ, Mecha M, et al., 2019, Manipulation of gut microbiota influences immune responses, axon preservation, and motor disability in a model of progressive multiple sclerosis. Front Immunol, 10: 1374. https://doi.org/10.3389/fimmu.2019.01374

 

  1. Gödel C, Kunkel B, Kashani A, et al., 2020, Perturbation of gut microbiota decreases susceptibility but does not modulate ongoing autoimmune neurological disease. J Neuroinflammation, 17: 79. https://doi.org/10.1186/s12974-020-01766-9

 

  1. Chen H, Ma X, Liu Y, et al., 2019, Gut microbiota interventions with Clostridium butyricum and norfloxacin modulate immune response in experimental autoimmune encephalomyelitis mice. Front Immunol, 10: 1662. https://doi.org/10.3389/fimmu.2019.01662

 

  1. Minagar A, Alexander JS, Schwendimann RN, et al., 2008, Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: An open-label trial. Arch Neurol, 65: 199–204. https://doi.org/10.1001/archneurol.2007.41

 

  1. Mazdeh M, Mobaien AR, 2012, Efficacy of doxycycline as add-on to interferon beta-1a in treatment of multiple sclerosis. Iran J Neurol, 11: 70–73.

 

  1. Metz LM, Eliasziw M, 2017, Trial of minocycline in clinically isolated syndrome of multiple sclerosis. N Engl J Med, 377: 789. https://doi.org/10.1056/NEJMc1708486

 

  1. Ross CL, Spinler JK, Savidge TC, 2016, Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection. Anaerobe, 41: 37–43. https://doi.org/10.1016/j.anaerobe.2016.05.006

 

  1. Zmora N, Suez J, Elinav E, 2019, You are what you eat: Diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol, 16: 35–56. https://doi.org/10.1038/s41575-018-0061-2

 

  1. Sonnenburg ED, Smits SA, Tikhonov M, et al., 2016, Diet-induced extinctions in the gut microbiota compound over generations. Nature, 529: 212–215. https://doi.org/10.1038/nature16504

 

  1. Sonnenburg JL, Backhed F, 2016, Diet-microbiota interactions as moderators of human metabolism. Nature, 535: 56–64. https://doi.org/10.1038/nature18846

 

  1. Kap YS, Bus-Spoor C, van Driel N, et al., 2018, Targeted diet modification reduces multiple sclerosis-like disease in adult marmoset monkeys from an outbred colony. J Immunol, 201: 3229–3243. https://doi.org/10.4049/jimmunol.1800822

 

  1. Cignarella F, Cantoni C, Ghezzi L, et al., 2018, Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab, 27: 1222–1235.e6. https://doi.org/10.1016/j.cmet.2018.05.006

 

  1. Saresella M, Mendozzi L, Rossi V, et al., 2017, Immunological and clinical effect of diet modulation of the gut microbiome in multiple sclerosis patients: A pilot study. Front Immunol, 8: 1391. https://doi.org/10.3389/fimmu.2017.01391

 

  1. Esposito S, Sparaco M, Maniscalco GT, et al., 2021, Lifestyle and Mediterranean diet adherence in a cohort of Southern Italian patients with Multiple Sclerosis. Mult Scler Relat Disord, 47: 102636, https://doi.org/10.1016/j.msard.2020.102636

 

  1. Kao D, Roach B, Silva M, et al., 2017, Effect of oral capsule-vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: A randomized clinical trial. JAMA, 318: 1985–1993. https://doi.org/10.1001/jama.2017.17077

 

  1. Cammarota G, Ianiro G, 2019, FMT for ulcerative colitis: Closer to the turning point. Nat Rev Gastroenterol Hepatol, 16: 266–268. https://doi.org/10.1038/s41575-019-0131-0

 

  1. El-Salhy M, Hatlebakk JG, Gilja OH, et al., 2020, Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut, 69: 859–867. https://doi.org/10.1136/gutjnl-2019-319630

 

  1. Stanisavljević S, Dinić M, Jevtić B, et al., 2018, Gut microbiota confers resistance of albino Oxford rats to the induction of experimental autoimmune encephalomyelitis. Front Immunol, 9: 942. https://doi.org/10.3389/fimmu.2018.00942

 

  1. Chitrala KN, Guan H, Singh NP, et al., 2017, CD44 deletion leading to attenuation of experimental autoimmune encephalomyelitis results from alterations in gut microbiome in mice. Eur J Immunol, 47: 1188–1199. https://doi.org/10.1002/eji.201646792

 

  1. Chen H, Shen L, Liu Y, et al., 2021, Strength exercise confers protection in central nervous system autoimmunity by altering the gut microbiota. Front Immunol, 12: 628629. https://doi.org/10.3389/fimmu.2021.628629

 

  1. Al-Ghezi ZZ, Busbee PB, Alghetaa H, et al., 2019, Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome. Brain Behav Immun, 82: 25–35. https://doi.org/10.1016/j.bbi.2019.07.028

 

  1. Lu XY, Han B, Deng X, et al., 2020, Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota. Gut Microbes, 12: 1857515. https://doi.org/10.1080/19490976.2020.1857515

 

  1. Engen PA, Zaferiou A, Rasmussen H, et al., 2020, Single-arm, non-randomized, time series, single-subject study of fecal microbiota transplantation in multiple sclerosis. Front Neurol, 11: 978. https://doi.org/10.3389/fneur.2020.00978
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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