Role of the intestinal microbiota in the pathogenesis of multiple sclerosis. Part 1. Clinical and experimental evidence for the involvement of the gut microbiota in the development of multiple sclerosis

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The review discusses the complex role of the intestinal microbiota in the pathogenesis of multiple sclerosis, summarizes data from studies of changes in the composition of the intestinal microbiome in patients with multiple sclerosis, and provides evidence of the involvement of the intestinal microbiota in the development of experimental autoimmune encephalomyelitis in animals, a valid model of multiple sclerosis.

About the authors

Irina N. Abdurasulova

Institute of Experimental Medicine

Author for correspondence.
Email: i_abdurasulova@mail.ru
ORCID iD: 0000-0003-1010-6768
SPIN-code: 5019-3940
Scopus Author ID: 22233604700

Cand. Sci. (Biol.), Head of the Pavlov Department of Physiology

Russian Federation, Saint Petersburg

References

  1. Lassmann H, Brück W, Lucchinetti C. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17(2):210–218. doi: 10.1111/j.1750-3639.2007.00064.x
  2. Kingwell E, Marriott JJ, Jette N, et al. Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC Neurol. 2013;13:128. doi: 10.1186/1471-2377-13-128
  3. Stys PK, Zamponi GW, van Minnen J, Geurts JJ. Will the real multiple sclerosis please stand up? Nat Rev Neurosci. 2012;13(7):507–514. doi: 10.1038/nrn3275
  4. Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 2010;9(5):520–532. doi: 10.1016/S1474-4422(10)70064-8
  5. Filippi M, Bar-Or A, Piehl F, et al. Multiple sclerosis. Nat Rev Dis Primers. 2018;4(1):43. doi: 10.1038/s41572-018-0041-4
  6. Dobson R. Giovannoni G. Multiple sclerosis — a review. Eur J Neurol. 2019;26(1):27–40. doi: 10.1111/ene.13819
  7. Orton SM, Herrera BM, Yee IM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol. 2006;5(11):932–936. doi: 10.1016/S1474-4422(06)70581-6
  8. Trojano M, Lucchese G, Graziano G, et al. Geographical variations in sex ratio trends over time in multiple sclerosis. PLoS One. 2012;7(10):e48078. doi: 10.1371/journal.pone.0048078
  9. Tomassini V, Pozzilli C. Sex hormone, brain damage and clinical course of multiple sclerosis. J Neurol Sci. 2009;286(1–2):35–39. doi: 10.1016/j.jns.2009.04.014
  10. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343(13):938–952. doi: 10.1056/NEJM200009283431307
  11. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–1517. doi: 10.1016/S0140-6736(08)61620-7
  12. Rovaris M, Confavreux C, Furlan R, et al. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol. 2006;5(4):343–354. doi: 10.1016/S1474-4422(06)70410-0
  13. Peterson JW, Trapp BD. Neuropathobiology of multiple sclerosis. Neurol Clin. 2005;23(1):107–129, vi-vii. doi: 10.1016/j.ncl.2004.09.008
  14. Levinthal DJ, Rahman F, Nusrat S, et al. Adding to the burden: gastrointestinal symptoms and syndromes in multiple sclerosis. Mult Scler Int. 2013;2013:319201. doi: 10.1155/2013/319201
  15. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: Pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J. 2017;19(1):1–10. doi: 10.22074/cellj.2016.4867
  16. Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338(5):278–285. doi: 10.1056/NEJM199801293380502
  17. Lucchinetti C, Brück W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000;47(6):707–717. doi: 10.1002/1531-8249(200006)47:6<707::aid-ana3>3.0.co;2-q
  18. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol. 2005;23:683–747. doi: 10.1146/annurev.immunol.23.021704.115707
  19. Frohman EM, Racke MK, Raine CS. Multiple sclerosis — the plaque and its pathogenesis. N Engl J Med. 2006;354(9):942–955. doi: 10.1056/NEJMra052130
  20. Frischer JM, Bramow S, Dal-Bianco A, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brain. Brain. 2009;132(Pt 5):1175–1189. doi: 10.1093/brain/awp070
  21. Weygandt M, Hackmack K, Pfüller C, et al. MRI pattern recognition in multiple sclerosis normal-appearing brain areas. PLoS One. 2011;6(6):e21138. doi: 10.1371/journal.pone.0021138
  22. Venken K, Hellings N, Broekmans T, et al. Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. J Immunol. 2008;180(9):6411–6420. doi: 10.4049/jimmunol.180.9.6411
  23. Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012;122(4):1180–1188. doi: 10.1172/JCI58649
  24. El Behi M, Dubucquoi S, Lefranc D, et al. New insights into cell responses involved in experimental autoimmune encephalomyelitis and multiple sclerosis. Immunol Lett. 2005;96(1):11–26. doi: 10.1016/j.imlet.2004.07.017
  25. Abdurasulova IN, Klimenko VM. The role of immune and glial cells in neurodegenerative processes. Medical Academic Journal. 2011;1:12–29. (In Russ.). doi: 10.17816/MAJ11112-29
  26. Abdurasulova IN, Klimenko VM. Heterogeneity of the mechanisms of nerve cell damage in demyelinating autoimmune diseases of the CNS. J Neurosci Behav Physiol. 2011;41(4):364–374. doi: 10.1007/s11055-011-9424-7
  27. Miller E, Wachowicz B, Majsterek I. Advances in antioxidative therapy of multiple sclerosis. Curr Med Chem. 2013;20(37):4720–4730. doi: 10.2174/09298673113209990156
  28. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247–269. doi: 10.1146/annurev.neuro.30.051606.094313
  29. Weng M, Walker WA. The role of gut microbiota in programming the immune phenotype. J Dev Orig Health Dis. 2013;4(3):203–214. doi: 10.1017/S2040174412000712
  30. Wekerle H. Nature plus Nurture: the triggering of multiple sclerosis. Swiss Med Wkly. 2015;145:w14189. doi: 10.4414/smw.2015.14189
  31. Eftekharian MM, Sayad A, Omrani MD, et al. Single nucleotide polymorphism in the FOXP3 gene are associated with increased risk of relapsing-remitting multiple sclerosis. Hum Antibodies. 2016;24(3–4):85–90. doi: 10.3233/HAB-160299
  32. Wawrusiewicz-Kurylonek N, Chorąży M, Posmyk R, et al. The FOXP3 rs3761547 gene polymorphism in multiple sclerosis as a male-specific risk factor. Neuromolecular Med. 2018;20(4):537–543. doi: 10.1007/s12017-018-8512-z
  33. Bush WS, Sawcer SJ, de Jager PL, et al. Evidence for polygenic susceptibility to multiple sclerosis — the shape of things to come. Am J Hum Genet. 2010;86(4):621–625. doi: 10.1016/j.ajhg.2010.02.027
  34. International Multiple Sclerosis Genetics Consortium; Wellcome Trust Case Control Consortium 2; Sawcer S, Hellenthal G, Pirinen M, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–219. doi: 10.1038/nature10251
  35. Beecham AH, Patsopoulos NA, Xifara DK, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45(11):1353–1360. doi: 10.1038/ng.2770
  36. Lill CM, Luessi F, Alcina A, et al. Genome-wide significant association with seven novel multiple sclerosis risk loci. J Med Genet. 2015;52(12):848–855. doi: 10.1136/jmedgenet-2015-103442
  37. Wang JH, Pappas D, de Jager PL, et al. Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med. 2011;3(1):3. doi: 10.1186/gm217
  38. Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet. 2009;41(7):824–828. doi: 10.1038/ng.396
  39. International Multiple Sclerosis Genetics Consortium: Patsopoulos NA, Baranzini SE, Santaniello A, et al. The multiple sclerosis genomic map: Role of peripheral immune cells and resident microglia in susceptibility. bioRxiv. 2017. doi: 10.1101/143933
  40. Lioudyno V, Abdurasulova I, Bisaga G, et al. Single nucleotide polymorphism rs948854 in human galanin gene and multiple sclerosis: a gender-specific risk factor. J Neurosci Res. 2017;95(1–2):644–651. doi: 10.1002/jnr.23887
  41. Lioudyno V, Abdurasulova I, Tatarinov A, et al. The effect of galanin gene polymorphism RS948854 on the severity of multiple sclerosis course: a significant association with the age of onset. Mult Scler Relat Disord. 2020;37:101439. doi: 10.1016/j.msard.2019.101439
  42. Lioudyno V, Abdurasulova I, Negoreeva I, et al. Common genetic variant rs2821557 in KCNA3 is linked to a severity of multiple sclerosis. J Neurosci Res. 2021;99(1):200–208. doi: 10.1002/jnr.24596
  43. Mumford CJ, Wood NW, Kellar-Wood H, et al. The British Isles survey of multiple sclerosis in twins. Neurology. 1994;44(1):11–15. doi: 10.1212/wnl.44.1.11
  44. Willer CJ, Dyment DA, Risch NJ, et al. Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci USA. 2003;100(22):12877–12882. doi: 10.1073/pnas.1932604100
  45. Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017;13(1):25–36. doi: 10.1038/nrneurol.2016.187
  46. Leibowitz U, Antonovsky A, Medalie JM, et al. Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation. J Neurol Neurosurg Psychiatry. 1966;29(1):60–68. doi: 10.1136/jnnp.29.1.60
  47. Alotaibi S, Kennedy J, Tellier R, et al. Epstein-barr virus in pediatric multiple sclerosis. JAMA. 2004;291(15):1875–1879. doi: 10.1001/jama.291.15.1875
  48. Munger KL, Levin LI, Hollis BW, et al. Serum 25-Hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296(23):2832–2838. doi: 10.1001/jama.296.23.2832
  49. Spelman T, Gray O, Trojano M, et al. Seasonal variation of relapse rate in multiple sclerosis is latitude dependen. Ann Neurol. 2014;76(6):880–890. doi: 10.1002/ana.24287
  50. Ascherio A, Munger KL, White R, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 2014;71(3):306–314. doi: 10.1001/jamaneurol.2013.5993
  51. Farez MF, Fiol MP, Gaitán MI, et al. Sodium intake is associated with increased disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2015;86(1):26–31. doi: 10.1136/jnnp-2014-307928
  52. Bagur MJ, Murcia MA, Jimenez-Monreal AM, et al. Influence of diet in multiple sclerosis: a systematic review. Adv Nutr. 2017;8(3):463–472. doi: 10.3945/an.116.014191
  53. Hedström AK, Alfredsson L, Olsson T. Environmental factors and their interactions with risk genotypes in MS susceptibility. Curr Opin Neurol. 2016;29(3):293–298. doi: 10.1097/WCO.0000000000000329
  54. Mohr DC. Stress and multiple sclerosis. J Neurol. 2007;254 Suppl 2:II65–II68. doi: 10.1007/s00415-007-2015-4
  55. Artemiadis AK, Anagnostouli MC, Alexopoulos EC. Stress as a risk factor for multiple sclerosis onset or relapse: a systematic review. Neuroepidemiology. 2011;36(2):109–120. doi: 10.1159/000323953
  56. Hawkes CH. Smoking is a risk factor for multiple sclerosis: a meta-analysis. Mult Scler. 2007;13(5):610–615. doi: 10.1177/1352458506073501
  57. Jafari N, Hintzen RQ. The association between cigarette smoking and multiple sclerosis. J Neurol Sci. 2011;311(1–2):78–85. doi: 10.1016/j.jns.2011.09.008
  58. Munger KL. Childhood obesity is a risk factor for multiple sclerosis. Mult Scler. 2013;19(13):1800. doi: 10.1177/1352458513507357
  59. Jahanfar S, Duggan T, Tkachuk S, Tremlett H. Factors associated with onset, relapses or progression in multiple sclerosis: a systematic review. Neurotoxicology. 2017;61:189–212. doi: 10.1016/j.neuro.2016.03.020
  60. Granieri E, Casetta I, Tola MR, Ferrante P. Multiple sclerosis: infectious hypothesis. Neurol Sci. 2001;22(2):179–185. doi: 10.1007/s100720170021
  61. Haegert DG. The initiation of multiple sclerosis: a new infectious hypothesis. Med Hypotheses. 2003;60(2):165–170. doi: 10.1016/s0306-9877(02)00349-3
  62. Challoner PB, Smith KT, Parker JD, et al. Plaque associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci USA. 1995;92(16):7440–7444. doi: 10.1073/pnas.92.16.7440
  63. Soldan SS, Berti R, Salem N, et al. Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA. Nat Med. 1997;3(12):1394–1397. doi: 10.1038/nm1297-1394
  64. Ascherio A, Munch M. Epstein–Barr virus and multiple sclerosis. Epidemiology. 2000;11(2):220–224. doi: 10.1097/00001648-2000030000-00023
  65. Fierz W. Multiple sclerosis: an example of pathogenic viral interaction? Virol J. 2017;14(1):42. doi: 10.1186/s12985-017-0719-3
  66. Antony JM, DesLauriers AM, Bhat RK, et al. Human endogenous retroviruses and multiple sclerosis: Innocent bystanders or disease determinants? Biochim Biophys Acta. 2011;1812(2):162–176. doi: 10.1016/j.bbadis.2010.07.016
  67. Bahar M, Ashtari F, Aghaei M, et al. Mycoplasma pneumonia seroposivity in Iranian patients with relapsing-remitting multipl sclerosis: a randomized case-control study. J Pak Med Assoc. 2012;62(3 Suppl 2):S6–8.
  68. Munger KL, Peeling RW, Hernan MA. Infection with Chlamydia pneumoniae and risk of multiple sclerosis. Epidemiology. 2003;14(2):141–147. doi: 10.1097/01.EDE.0000050699.23957.8E
  69. Buljevac D, Flach HZ, Hop WC, et al. Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain. 2002;125(Pt 5):952–960. doi: 10.1093/brain/awf098
  70. Steelman AJ. Infection as an environmental trigger of multiple sclerosis disease exacerbation. Front Immunol. 2015;6:520. doi: 10.3389/fimmu.2015.00520
  71. Kurtzke JF. A reassessment of the distribution of multiple sclerosis. Part one. Acta Neurol Scand. 1975;51(2):110–136. doi: 10.1111/j.1600-0404.1975.tb01364.x
  72. Browne P, Chandraratna D, Angood C, et al. Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity. Neurology. 2014;83(11):1022–1024. doi: 10.1212/WNL.0000000000000768
  73. Osoegawa M, Kira J, Fukazawa T, et al. Temporal changes and geographical differences in multiple sclerosis phenotypes in Japanese: nationwide survey results over 30 years. Mult Scler. 2009;15(2):159–173. doi: 10.1177/1352458508098372
  74. Houzen H, Niino M, Hata D, et al. Increasing prevalence and incidence of multiple sclerosis in northern Japan. Mult Scler. 2008;14(7):887–892. doi: 10.1177/1352458508090226
  75. Jancic J, Nikolic B, Ivancevic N, et al. Multiple sclerosis in pediatrics: current concepts and treatment options. Neurol Ther. 2016;5(2):131–143. doi: 10.1007/s40120-016-0052-6
  76. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299(6710):1259–1260. doi: 10.1136/bmj.299.6710.1259
  77. Fleming J, Fabry Z. The hygiene hypothesis and multiple sclerosis. Ann Neurol. 2007;61(2):85–89. doi: 10.1002/ana.21092
  78. Krone B, Grange JM. Paradigms in multiple sclerosis: time for a change, time for a unifying concept. Inflammopharmacol. 2011;19(4):187–195. doi: 10.1007/s10787-011-0084-6
  79. Nielsen TR, Rostgaard K, Nielsen NM, et al. Multiple sclerosis after infectious mononucleosis. Arch Neurol. 2007;64(1):72–75. doi: 10.1001/archneur.64.1.72
  80. Esposito S, Bonavita S, Sparaco M, et al. The role of diet in multiple sclerosis: a review. Nutr Neurosci. 2018;21(6):377–390. doi: 10.1080/1028415X.2017.1303016
  81. Kira J, Yamasaki K, Horiuchi I, et al. Changes in the clinical phenotypes of multiple sclerosis during the past 50 years in Japan. J Neurol Sci. 1999;166(1):53–57. doi: 10.1016/s0022-510x(99)00115-x
  82. Gimeno D, Kivimäki M, Brunner EJ, et al. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med. 2009;39(3):413–423. doi: 10.1017/S0033291708003723
  83. Berer K, Krishnamoorthy G. Commensal gut flora and brain autoimmunity: a love or hate affair? Acta Neuropathol. 2012;123(5):639–651. doi: 10.1007/s00401-012-0949-9
  84. Brown J, Quattrochi B, Everett C, et al. Gut commensals, dysbiosis, and immune response imbalance in the pathogenesis of multiple sclerosis. Mult Scler. 2021;27(6):807–811. doi: 10.1177/1352458520928301
  85. Barcellos LF, Oksenberg JR, Green AJ, et al. Genetic basic for clinical expression in multiple sclerosis. Brain. 2002;125(Pt 1):150–158. doi: 10.1093/brain/awf009
  86. Imani D, Azimi A, Salehi Z, et al. Association of nod-like receptor protein-3 single nucleotide gene polymorphisms and expression with the susceptibility to relapsing–remitting multiple sclerosis. Int J Immunogenet. 2018;45(6):329–336. doi: 10.1111/iji.12401
  87. Racke MK, Drew PD. Toll-like receptors in multiple sclerosis. Curr Top Microbiol Immunol. 2009;336:155–168. doi: 10.1007/978-3-642-00549-7_9
  88. Gharagozloo M, Gris KV, Mahvelati T, et al. NLR-dependent regulation of inflammation in multiple sclerosis. Front Immunol. 2018;8:2012. doi: 10.3389/fimmu.2017.02012
  89. Maghzi A-H, Etemadifar M, Heshmat-Ghahdarijani K, et al. Cesarean delivery may increase the risk of multiple sclerosis. Mult Scler. 2012;18(4):468–471. doi: 10.1177/1352458511424904
  90. Nielsen NM, Bager P, Stenager E, et al. Cesarean section and offspring’s risk of multiple sclerosis: a Danish nationwide cohort study. Mult Scler. 2013;19(11):1473–1477. doi: 10.1177/1352458513480010
  91. Conradi S, Malzahn U, Paul F, et al. Breastfeeding is associated with lower risk for multiple sclerosis. Mult Scler. 2013;19(5):553–558. doi: 10.1177/1352458512459683
  92. Ragnedda G, Leoni S, Parpinel M, et al. Reduced duration of breastfeeding is associated with a higher risk of multiple sclerosis in both Italian and Norwegian adult males: the EnvIMS study. J Neurol. 2015;262(5):1271–1277. doi: 10.1007/s00415-015-7704
  93. Kleinewietfeld M, Manzel A, Titze J, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013;496(7446):518–522. doi: 10.1038/nature11868
  94. Sedaghat F, Jessri M, Behrooz M, et al. Mediterranean diet adherence and risk of multiple sclerosis: a case-control study. Asia Pac J Clin Nutr. 2016;25(2):377–384. doi: 10.6133/apjcn.2016.25.2.12
  95. Andeweg SP, Keşmir C, Dutilh BE. Quantifying the impact of human leukocyte antigen on the human gut microbiota. mSphere. 2021;6(4):e00476–21. doi: 10.1128/mSphere.00476-21
  96. Carvalho FA, Koren O, Goodrich JK, et al. Transient inability to manage Proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe. 2012;12(2):139–152. doi: 10.1016/j.chom.2012.07.004
  97. Knights D, Silverberg MS, Weersma RK, et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med. 2014;6(12):107. doi: 10.1186/s13073-014-0107-1
  98. Wang J, Thingholm LB, Skiecevičienė J, et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat Genet. 2016;48(11):1396–1406. doi: 10.1038/ng.3695
  99. Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17(5):690–703. doi: 10.1016/j.chom.2015.04.004
  100. Ma J, Li Z, Zhang W, et al. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants. Sci Rep. 2020;10(1):15792. doi: 10.1038/s41598-020-72635-x
  101. Mueller S, Saunier K, Hanisch C, et al. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol. 2006;72(2):1027–1033. doi: 10.1128/AEM.72.2.1027-1033.2006
  102. Singh P, Manning SD. Impact of age and sex on the composition and abundance of the intestinal microbiota in individuals with and without enteric infections. Ann Epidemiol. 2016;26(5):380–385. doi: 10.1016/j.annepidem.2016.03.007
  103. Sinha T, Vich Vila A, Garmaeva S, et al. Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles. Gut Microbes. 2019;10(3):358–366. doi: 10.1080/19490976.2018.1528822
  104. Koliada A, Moseiko V, Romanenko M, et al. Sex differences in the phylum-level human gut microbiota composition. BMC Microbiol. 2021;21(1):131. doi: 10.1186/s12866-021-02198-y
  105. Carvalho-Queiroz С, Johansson MA, Persson J-O, et al. Associations between EBV and CMV seropositivity, early exposures, and gut microbiota in a prospective birth cohort: A 10-Year follow-up. Front Pediatr. 2016;4:93. doi: 10.3389/fped.2016.00093
  106. Hollins SL, Hodgson DM. Stress, microbiota, and immunity. Curr Opin Behav Sci. 2019;28:66–71. doi: 10.1016/j.cobeha.2019.01.015
  107. De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010;107(33):14691–14696. doi: 10.1073/pnas.1005963107
  108. Merra G, Noce A, Marrone G, et al. Influence of mediterranean diet on human gut microbiota. Nutrients. 2021;13(1):7. doi: 10.3390/nu13010007
  109. Lee SH, Yun Y, Kim SJ, et al. Association between cigarette smoking status and composition of gut microbiota: Population-based cross-sectional study. J Clin Med. 2018;7(9):282. doi: 10.3390/jcm7090282
  110. Bervoets L, Van Hoorenbeeck K, Kortleven I, et al. Differences in gut microbiota composition between obese and lean children: a cross-sectional study. Gut Pathog. 2013;5(1):10. doi: 10.1186/1757-4749-5-10
  111. Riva A, Borgo F, Lassandro C, et al. Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol. 2017;19(1):95–105. doi: 10.1111/1462-2920.13463
  112. Bora SA, Kennett MJ, Smith PB, et al. The gut microbiota regulates endocrine vitamin D methabolism through fibroblast growth factor 23. Front Immunol. 2018;9:408. doi: 10.3389/fimmu.2018.00408
  113. Tabatabaeizadeh SA, Tafazoli N, Ferns GA, et al. Vitamin D, the gut microbiome and inflammatory bowel disease. J Res Med Sci. 2018;23:75. doi: 10.4103/jrms.JRMS_606_17
  114. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature. 2007;449(7164):804–810. doi: 10.1038/nature06244
  115. Mai V, Draganov PV. Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health. World J Gastroenterol. 2009;15(1):81–85. doi: 10.3748/wjg.15.81
  116. Lankelma JM, Nieuwdorp M, de Vos WM, Wiersinga WJ. The gut microbiota in internal medicine: implications for health and disease. Neth J Med. 2015;73(2):61–68.
  117. Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–230. doi: 10.1038/nature11550
  118. McDermott AJ, Huffnagle GB. The microbiome and regulation of mucosal immunity. Immunology. 2014;142(1):24–31. doi: 10.1111/imm.12231
  119. Bäckhed F, Ley RE, Sonnenburg JL, et al. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–1920. doi: 10.1126/science.1104816
  120. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–1638. doi: 10.1126/science.1110591
  121. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol. 2016;14(1):20–32. doi: 10.1038/nrmicro3552
  122. Schippa S, Conte MP. Dysbiotic events in gut microbiota: impact on human health. Nutrients. 2014;6(12):5786–5805. doi: 10.3390/nu6125786
  123. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124(4):837–848. doi: 10.1016/j.cell.2006.02.017
  124. Bianconi E, Piovesan A, Facchin F, et al. An estimation of the number of cells in the human body. Ann Hum Biol. 2013;40(6):463–471. doi: 10.3109/03014460.2013.807878
  125. Khanna S, Tosh PK. A clinician’s primer on the microbiome in human health and disease. Mayo Clin Proc. 2014;89(1):107–114. doi: 10.1016/j.mayocp.2013.10.011
  126. Brestoff JR, Artis D. Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol. 2013;14(7):676–684. doi: 10.1038/ni.2640
  127. Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312(5778):1355–1359. doi: 10.1126/science.1124234
  128. Hollister EB, Gao C, Versalovic J. Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology. 2014;146(6):1449–1458. doi: 10.1053/j.gastro.2014.01.052
  129. Hood L. Tackling the microbiome. Science. 2012;336(6086):1209. doi: 10.1126/science.1225475
  130. Strober W. Inside the microbial and immune labyrinth: gut microbes: friends or fiends? Nat Med. 2010;16(11):1195–1197. doi: 10.1038/nm1110-1195
  131. Cerf-Bensussan N, Gaboriau-Routhiau V. The immune system and the gut microbiota: friends or foes? Nat Rev Immunol. 2010;10(10):735–744. doi: 10.1038/nri2850
  132. Benson AK, Kelly SA, Legge R, et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci USA. 2010;107(44):18933–18938. doi: 10.1073/pnas.1007028107
  133. Xu J, Mahowald M, Ley R, et al. Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol. 2007;5(7):e156. doi: 10.1371/journal.pbio.0050156
  134. Quigley EMM. Gut bacteria in health and disease. Gastroenterol Hepatol (NY). 2013;9(9):560–569.
  135. Macfarlane S, Macfarlane GT. Composition and metabolic activities of bacterial biofilms colonizing food residues in the human gut. Appl Environ Microbiol. 2006;72(9):6204–6211. doi: 10.1128/AEM.00754-06
  136. Van der Waaij LA, Harmsen HJ, Madjipour M, et al. Bacterial population analysis of human colon and terminal ileum biopsies with 16S rRNA-based fluorescent probes: commensal bacteria live in suspension and have no direct contact with epithelial cells. Inflamm Bowel Dis. 2005;11(10):865–871. doi: 10.1097/01.mib.0000179212.80778.d3
  137. Swidsinski A, Loening-Baucke V, Theissig F, et al. Comparative study of the intestinal mucus barrier in normal and inflamed colon. Gut. 2007;56(3):343–350. doi: 10.1136/gut.2006.098160
  138. Carroll IM, Ringel-Kulka T, Keku TO, et al. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G799–807. doi: 10.1152/ajpgi.00154.2011
  139. Atuma C, Strugala V, Allen A, Holm L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol. 2001;280(5):G922–G929. doi: 10.1152/ajpgi.2001.280.5.G922
  140. Johansson ME, Phillipson M, Petersson J, et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci USA. 2008;105(39):15064–15069. doi: 10.1073/pnas.0803124105
  141. Gordon HA, Pesti L. The gnotobiotic animal as a tool in the study of host microbial relationship. Bacteriol Rev. 1971;35(4):390–429. doi: 10.1128/br.35.4.390-429.1971
  142. Falk PG, Hooper LV, Midtverd T, Gordon JI. Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology. Microbiol Mol Biol Rev. 1998;62(4):1157–1170. doi: 10.1128/MMBR.62.4.1157-1170.1998
  143. Sjögren YM, Tomicic S, Lundberg A, et al. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clin Exp Allergy. 2009;9(12):1842–1851. doi: 10.1111/j.1365-2222.2009.03326.x
  144. Martin R, Nauta AJ, Ben Amor K, et al. Early life: Gut microbiota and immune development in infancy. Benef Microbes. 2010;1(4):367–382. doi: 10.3920/BM2010.0027
  145. Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451–1463. doi: 10.1016/j.cell.2013.11.024
  146. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunoregulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122(1):107–118. doi: 10.1016/j.cell.2005.05.007
  147. Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe. 2015;17(5):565–576. doi: 10.1016/j.chom.2015.04.011
  148. 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. doi: 10.1126/scitranslmed.3009759
  149. Hoban AE, Stilling RM, Ryan FJ, et al. Regulation of prefrontal cortex myelination by the microbiota. Transl Psychiatry. 2016;6(4):e774. doi: 10.1038/tp.2016.42
  150. Sassone-Corsi M, Raffatellu M. No vacancy: how beneficial microbes cooperate with immunity to provide colonization resistance to pathogens. J Immunol. 2015;194(9):4081–4087. doi: 10.4049/jimmunol.1403169
  151. Hansen NW, Sams A. The Microbiotic highway to health — new perspective on food structure, gut microbiota, and host inflammation. Nutrients. 2018;10(11):1590. doi: 10.3390/nu10111590
  152. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512–519. doi: 10.1016/S0140-6736(03)12489-0
  153. Sekirov I, Russell SL, Antunes LCM, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904. doi: 10.1152/physrev.00045.2009
  154. Sommer F, Bäckhed F. The gut microbiota — Masters of host development and physiology. Nat Rev Microbiol. 2013;11(4):227–238. doi: 10.1038/nrmicro2974
  155. Rojo D, Méndez-García C, Raczkowska BA, et al. Exploring the human microbiome from multiple perspectives: factors altering its composition and function. FEMS Microbiol Rev. 2017;41(4):453–478. doi: 10.1093/femsre/fuw046
  156. Cantarel BL, Waubant E, Chehoud C, et al. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med. 2015;63(5):729–734. doi: 10.1097/JIM.0000000000000192
  157. Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belondind to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429. doi: 10.1371/journal.pone.0137429
  158. Chen J, Chia N, Kalari KR, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep. 2016;6:28484. doi: 10.1038/srep28484
  159. Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015. doi: 10.1038/ncomms12015
  160. Tremlett H, Fadrosh DW, Faruqi AA, et al. Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. BMC Neurol. 2016;16(1):182. doi: 10.1186/s12883-016-0703-3
  161. 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):10719–10724. doi: 10.1073/pnas.1711233114
  162. Cekanaviciute E, Yoo BB, Runia TF, 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(40):10713–10718. doi: 10.1073/pnas.1711235114
  163. 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. doi: 10.1126/sciadv.1700492
  164. Cekanaviciute E, Pröbstel A-K, Thomann A, et al. Multiple sclerosis-associated changes in the composition and immune functions of spore-forming bacteria. mSystems. 2018;3(6):e00083–18. doi: 10.1128/mSystems.00083-18
  165. Forbes JD, Chen C-Y, Knox NC, et al. A comparative study of the gut microbiota in immune-mediated inflammatory diseases — does a common dysbiosis exist? Microbiome. 2018;6(1):221. doi: 10.1186/s40168-018-0603-4
  166. Abdurasulova IN, Matsulevich AV, Tarasova EA, et al. Changes of intestinal microbiome in multiple sclerosis are associated with immune shift and psychoemotional disorders. Medical Academic Journal. 2019;19(1S):51–54. doi: 10.17816/MAJ191S151-54
  167. Kozhieva M, Naumova N, Alikina T, et al. Primary progressive multiple sclerosis in a Russian cohort: relationship with gut bacterial diversity. BMC Microbiol. 2019;19(1):309. doi: 10.1186/s12866-019-1685-2
  168. Oezguen N, Yalcinkaya N, Kücükali CI, et al. Microbiota stratification identifies disease-specific alterations in neuro-Behçet’s disease and multiple sclerosis. Clin Exp Rheumatol. 2019;37 Suppl 121(6):58–66.
  169. Sand IK, Zhu Y, Ntranos A, et al. Disease-modifying therapies alter gut microbial composition in MS. Neurol Neuroimmunol Neuroinflamm. 2019;6(1):e517. doi: 10.1212/NXI.0000000000000517
  170. Storm-Larsen C, Myhr K-M, Farbu E, et al. Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis — a pilot trial. Mult Scler J Exp Transl Clin. 2019;5(4):2055217319888767. doi: 10.1177/2055217319888767
  171. Ventura RE, Iizumi1 T, Battaglia T, et al. Gut microbiome of treatment-naïve MS patients of different ethnicities early in disease course. Sci Rep. 2019;9(1):16396. doi: 10.1038/s41598-019-52894-z
  172. Zeng Q, Gong J, Liu X, et al. Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis. Neurochem Int. 2019;129:104468. doi: 10.1016/j.neuint.2019.104468
  173. 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). 2021;36(7):495–503. doi: 10.1016/j.nrleng.2020.05.006
  174. Kishikawa T, Ogawa K, Motooka D, et al. A Metagenome-wide association study of gut microbiome in patients with multiple sclerosis revealed novel disease pathology. Front Cell Infect Microbiol. 2020;10:585973. doi: 10.3389/fcimb.2020.585973
  175. Ling Z, Cheng Y, Yan X, et al. Alterations of the fecal microbiota in Chinese patients with multiple sclerosis. Front Immunol. 2020;11:590783. doi: 10.3389/fimmu.2020.590783
  176. Reynders T, Devolder L, Valles-Colomer M, et al. Gut microbiome variation is associated to Multiple Sclerosis phenotypic subtypes. Ann Clin Transl Neurol. 2020;7(4):406–419. doi: 10.1002/acn3.51004
  177. Takewaki D, Suda W, Sato W, et al. Alterations of the gut ecological and functional microenvironment in different stages of multiple sclerosis. PNAS. 2020;117(36):22402–22412. doi: 10.1073/pnas.2011703117
  178. Ní Choileáin S, Kleinewietfeld M, Raddassi K, et al. CXCR3+ T cells in multiple sclerosis correlate with reduced diversity of the gut microbiota. J Translat Autoimmun. 2020;3:100032. doi: 10.1016/j.jtauto.2019.100032
  179. Cox LM, Maghzi AH, Liu S, et al. The gut microbiome in progressive multiple sclerosis. Ann Neurol. 2021;89(6):1195–1211. doi: 10.1002/ana.26084
  180. Galluzzo P, Capri FC, Vecchioni L, et al. Comparison of the intestinal microbiome of Italian patients with multiple sclerosis and their household relatives. Life (Basel). 2021;11(7):620. doi: 10.3390/life11070620
  181. Pellizoni FP, Leite AZ, de Campos Rodrigues N, et al. Detection of dysbiosis and increased intestinal permeability in Brazilian patients with relapsing-remitting multiple sclerosis. Int J Environ Res Public Health. 2021;18(9):4621. doi: 10.3390/ijerph18094621
  182. Tremlett H, Zhu F, Arnold D, et al. The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes. Ann Clin Transl Neurol. 2021;8(12):2252–2269. doi: 10.1002/acn3.51476
  183. Yadav M, Ali S, Shrode RL, et al. Multiple sclerosis patients have an altered gut mycobiome and increased fungal to bacterial richness. bioRxiv. 2022;17(4):e0264556. doi: 10.1101/2021.08.30.458212
  184. Vallino A, Dos Santos A, Mathe CV, et al. Gut bacteria Akkermansia elicit a specific IgG response in CSF of patients with MS. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e688. doi: 10.1212/NXI.0000000000000688
  185. Hirano A, Umeno J, Okamoto Y, et al. Comparison of the microbial community structure between inflamed and non-inflamed sites in patients with ulcerative colitis. J Gastroenterol Hepatol. 2018;33(9):1590–1597. doi: 10.1111/jgh.14129
  186. Rumah KR, Linden J, Fischetti VA, Vartanian T. 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. 2013;8(10):e76359. doi: 10.1371/journal.pone.0076359
  187. Abdurasulova IN, Tarasova EA, Ermolenko EI, et al. Multiple sclerosis is associated with altered quantitative and qualitative composition of intestinal microbiota. Medical Academic Journal. 2015;15(3):55–67. (In Russ.)
  188. Mete A, Garcia J, Ortega J, et al. Brain lesions associated with clostridium perfringens type D epsilon toxin in a Holstein heifer calf. Vet Pathol. 2013;50(5):765–768. doi: 10.1177/0300985813476058
  189. Dorca-Arévalo J, Soler-Jover A, Gibert M, et al. Binding of epsilon-toxin from Clostridium perfringens in the nervous system. Vet Microbiol. 2008;131:14–25. doi: 10.1371/journal.pone.0102417
  190. Lonchamp E, Dupont J-L, Wioland L, et al. Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release. PLoS One. 2010;5(9):e13046. doi: 10.1371/journal.pone.0013046
  191. Finnie JW, Blumbergs PC, Manavis J. Neuronal damage produced in rat brains by Clostridium perfringens type D epsilon toxin. J Comp Pathol. 1999;120(4):415–420. doi: 10.1053/jcpa.1998.0289
  192. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–227. doi: 10.1038/nature11053
  193. Abdurasulova IN, Tarasova EA, Nikiforova IG, et al. The intestinal microbiota composition in patients with multiple sclerosis receiving different disease-modifying therapies (DMT). Korsakov Journal of Neurology and Psychiatry. 2018;118(8–2):62–69. (In Russ.). doi: 10.17116/jnevro201811808262
  194. Tarasova EA, Lioudyno VI, Matsulevich AV, et al. Features of the intestinal microbiota composition in multiple sclerosis patients receiving oral disease-modifying therapy. Medical Academic Journal. 2021;21(4):47–56. doi: 10.17816/MAJ88595
  195. Buscarinu MC, Fornasiero A, Romano S, et al. The contribution of gut barrier changes to multiple sclerosis pathophysiology. Front Immunol. 2019;10:1916. doi: 10.3389/fimmu.2019.01916
  196. Hermann-Bank ML, Skovgaard K, Stockmarr A, et al. The Gut Microbiotassay: a high-throughput qPCR approach combinable with next generation sequencing to study gut microbial diversity. BMC Genomics. 2013;14:788. doi: 10.1186/1471-2164-14-788
  197. Bang S, Yoo DA, Kim S-J, et al. Establishment and evaluation of prediction model for multiple disease classification based on gut microbial data. Sci Rep. 2019;9(1):10189. doi: 10.1038/s41598-019-46249-x
  198. Gold R, Linington C, Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain. 2006;129(Pt 8):1953–1971. doi: 10.1093/brain/awl075
  199. Ben-Nun A, Kaushansky N, Kawakami N, et al. From classic to spontaneous and humanized models of multiple sclerosis: Impact on understanding pathogenesis and drug development. J Autoimmun. 2014;54:33–50. doi: 10.1016/j.jaut.2014.06.004
  200. Krishnamoorthy G, Lassmann H, Wekerle H, Holz A. Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin Invest. 2006;116(9):2385–2392. doi: 10.1172/JCI28330
  201. Ochoa-Reparaz J, Mielcarz DW, Ditrio LE, et al. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol. 2009;183(10):6041–6050. doi: 10.4049/jimmunol.0900747
  202. Goverman J, Woods A, Larson L, et al. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell. 1993;72(4):551–560. doi: 10.1016/0092-8674(93)90074-z
  203. Berer K, Mues M, Koutrolos M, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479(7374):538–541. doi: 10.1038/nature10554
  204. Ivanov II, Frutos Rde L, Manel N, et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008;4(4):337–349. doi: 10.1016/j.chom.2008.09.009
  205. Ivanov II, Atarashi K, Manel N, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(3):485–498. doi: 10.1016/j.cell.2009.09.033
  206. Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responces to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA. 2011;108 Suppl 1(Suppl 1):4615–4622. doi: 10.1073/pnas.1000082107
  207. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775–787. doi: 10.1016/j.cell.2008.05.009
  208. 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):12204–12209. doi: 10.1073/pnas.0909122107
  209. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9(5):313–323. doi: 10.1038/nri2515
  210. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258–1270. doi: 10.1016/j.cell.2012.01.035
  211. Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne). 2020;11:25. doi: 10.3389/fendo.2020.00025
  212. Gandy K, Zhang J, Nagarkatti P, Nagarkatti M. The role of gut microbiota in shaping the relapse-remitting and chronic-progressive forms of multiple sclerosis in mouse models. Sci Rep. 2019;9(1):6923. doi: 10.1038/s41598-019-43356-7
  213. Boyko AN, Favorova OO, Kulakova OG, Gusev EI. Epidemiology and etiology of multiple sclerosis. In: Multiple sclerosis. Ed. by E.I. Gusev, I.A. Zavalishin, A.N. Boyko. Moscow: Real Time; 2011. (In Russ.)

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Figure. Accordance of age-related changes in microbial diversity in the intestine (a) to the hypothetical time scale of events in the natural development of multiple sclerosis proposed by E. Granieri – M. Pugliatti and (b) modified by A.N. Boyko et al. [213]

Download (513KB)
Indexing metadata

Copyright (c) 2022 Eco-Vector



Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».