Effects of disease-modifying drugs in multiple sclerosis on the gut microbiome

Cover Page

Cite item

Full Text

Abstract

Over the past decade, the scientific research has shown that the community of microorganisms that inhabit the gut, known as the gut microbiota, is closely linked to human health and disease, in part as a result of its influence on the systemic immune responses. The accumulated evidence suggests that these effects on the immune system are significant in neuroinflammatory diseases such as multiple sclerosis, and that modulation of the gut microbiota may be a potential therapeutic target in these conditions. In recent years, more and more studies have been appearing devoted to the role of microbiota in the development of various pathological processes in the central nervous system, including multiple sclerosis, through the brain-gut axis. In this regard, the question of finding ways to influence the microbiome is interesting. In addition to the existing attempts through the use of probiotics and fecal microbiota transplantation, of particular interest is the search for other ways of influencing the microbiome, including the effect of multiple sclerosis modifying therapies on the microbiota’s composition. The purpose of this review is to summarize the current evidence investigating the effects of disease-modifying treatment on the gut microbiome.

About the authors

Мadina А. Omarova

Federal Center of Brain Research and Neurotechnologies; Pirogov Russian National Research Medical University

Author for correspondence.
Email: omarova.neurology@mail.ru
ORCID iD: 0000-0002-6744-2191
Russian Federation, Moscow; Moscow

Аleksey N. Boyko

Federal Center of Brain Research and Neurotechnologies; Pirogov Russian National Research Medical University

Email: boykoan13@gmail.com
ORCID iD: 0000-0002-2975-4151
SPIN-code: 9921-9109

MD, PhD, Professor

Russian Federation, Moscow; Moscow

References

  1. Global Health Metrics Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211–1259. doi: 10.1016/S0140-6736(17)32154-2
  2. Grytten N, Torkildsen O, Myhr KM. Time trends in the incidence and prevalence of multiple sclerosis in Norway during eight decades. Acta Neurol Scand. 2015;132(199):29–36. doi: 10.1111/ane.12428
  3. Filippi M, Rocca MA, Ciccarelli O, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016;15(3):292–303. doi: 10.1016/S1474-4422(15)00393-2
  4. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162–173. doi: 10.1016/S1474-4422(17)30470-2
  5. Glaser A, Stahmann A, Meissner T, et al. Multiple sclerosis registries in Europe: An updated mapping survey. Mult Scler Relat Disord. 2019;(27):171–178. doi: 10.1016/j.msard.2018.09.032
  6. McKay KA, Hillert J, Manouchehrinia A. Long-term disability progression of pediatric-onset multiple sclerosis. Neurology. 2019; 92(24):e2764–e2773. doi: 10.1212/WNL.0000000000007647
  7. Guillemin F, Baumann C, Epstein J, et al. Older age at multiple sclerosis onset is an independent factor of poor prognosis: A population-based cohort study. Neuroepidemiology. 2017; 48(3-4):179–187. doi: 10.1159/000479516
  8. Patsopoulos NA. Genetics of multiple sclerosis: An overview and new directions. Cold Spring Harb Perspect Med. 2018; 8(7):a028951. doi: 10.1101/cshperspect.a028951
  9. Belbasis L, Bellou V, Evangelou E, et al. Environmental risk factors and multiple sclerosis: An umbrella review of systematic reviews and meta-analyses. Lancet Neurol. 2015;14(3):263–273. doi: 10.1016/S1474-4422(14)70267-4
  10. Fleck AK, Schuppan D, Wiendl H, Klotz L. Gut-CNS-Axis as possibility to modulate inflammatory disease activity-implications for multiple sclerosis. Int J Mol Sci. 2017;18(7):1526. doi: 10.3390/ijms18071526
  11. Boziki MK, Kesidou E, Theotokis P, et al. Microbiome in MS; where are we, what we know and do not know. Brain Sci. 2020;10(4):234. doi: 10.3390/brainsci10040234
  12. Camara-Lemarroy CR, Metz L, Meddings JB, et al. The intestinal barrier in multiple sclerosis: Implications for pathophysiology and therapeutics. Brain. 2018;141(7):1900–1916. doi: 10.1093/brain/awy131
  13. 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. doi: 10.1371/journal.pone.0137429
  14. 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
  15. Tremlett H, Fadrosh DW, Faruqi AA, et al. Gut microbiota in early pediatric multiple sclerosis: A case-control study. Eur J Neurol. 2016;23(8):1308–1321. doi: 10.1111/ene.13026
  16. 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
  17. 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
  18. Бойко А.Н., Мельников М.В., Бойко О.В., и др. Исследование содержания маркеров микробиоты в цереброспинальной жидкости пациентов с рассеянным склерозом и радиологически изолированным синдромом // Неврология, нейропсихиатрия, психосоматика. 2021. Т. 13, № 1. С. 27–30. [Boyko AN, Melnikov MV, Boyko OV, et al. Study of the content of microbiota markers in cerebrospinal fluid of patients with multiple sclerosis and radiologically isolated syndrome. Neurol Neuropsychiatry Psychosomat. 2021;13(1):27–30. (In Russ).] doi: 10.14412/2074-2711-2021-1S-27-30
  19. Кожиева М.Х., Мельников М.В., Роговский В.С., и др. Микробиота человека и рассеянный склероз // Журнал неврологии и психиатрии им. С.С. Корсакова. 2017. Т. 117, № 10-2. С. 11–19. [Kozhieva MK, Melnikov MV, Rogovsky VS, et al. Human microbiota and multiple sclerosis. J Neurol Psychiatry S.S. Korsakov. 2017;117(10-2):11–19. (In Russ).] doi: 10.17116/jnevro201711710211-19
  20. 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
  21. Camara-Lemarroy CR, Metz L, Meddings JB, et al. The intestinal barrier in multiple sclerosis: Implications for pathophysiology and therapeutics. Brain. 2018;141(7):1900–1916. doi: 10.1093/brain/awy131
  22. Rumah KR, Vartanian TK, Fischetti VA. Oral multiple sclerosis drugs inhibit the in vitro growth of epsilon toxin producing gut bacterium, clostridium perfringens. Front Cell Infect Microbiol. 2017;(7):11. doi: 10.3389/fcimb.2017.00011
  23. Linden JR, Ma Y, Zhao B, et al. Clostridium perfringens epsilon toxin causes selective death of mature oligodendrocytes and central nervous system demyelination. MBio. 2015;6(3):e02513. doi: 10.1128/mBio.02513-14
  24. Sand KI, 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
  25. Giles EM, Stagg AJ. Type 1 interferon in the human intestine-a co-ordinator of the immune response to the microbiota. Inflamm Bowel Dis. 2017;23(4):524–533. doi: 10.1097/MIB.0000000000001078
  26. LeMessurier KS, Hacker H, Chi L, et al. Type I interferon protects against pneumococcal invasive disease by inhibiting bacterial transmigration across the lung. PLoS Pathog. 2013;9(11):e1003727. doi: 10.1371/journal.ppat.1003727
  27. Nakahashi-Oda C, Udayanga KG, Nakamura Y, et al. Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces. Nat Immunol. 2016;17(4):441–450. doi: 10.1038/ni.3345
  28. Castillo-Alvarez F, Perez-Matute P, Oteo JA, Marzo-Sola ME. The influence of interferon beta-1b on gut microbiota composition in patients with multiple sclerosis. Neurologia. 2021;36(7): 495–503. doi: 10.1016/j.nrleng.2020.05.006
  29. Aharoni R, Sonego H, Brenner O, et al. The therapeutic effect of glatiramer acetate in a murine model of inflammatory bowel disease is mediated by anti-inflammatory T-cells. Immunol Lett. 2007;112(2):110–119. doi: 10.1016/j.imlet.2007.07.009
  30. Yablecovitch D, Shabat-Simon M, Aharoni R, et al. Beneficial effect of glatiramer acetate treatment on syndecan-1 expression in dextran sodium sulfate colitis. J Pharmacol Exp Ther. 2011;337(2):391–399. doi: 10.1124/jpet.110.174276
  31. Shahi SK, Freedman SN, Murra AC, et al. Prevotella histicola, a human gut commensal, is as potent as COPAXONE(R) in an animal model of multiple sclerosis. Front Immunol. 2019;(10):462. doi: 10.3389/fimmu.2019.00462
  32. 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
  33. Ma N, Wu Y, Xie F, et al. Dimethyl fumarate reduces the risk of mycotoxins via improving intestinal barrier and microbiota. Oncotarget. 2017;8(27):44625–44638. doi: 10.18632/oncotarget.17886
  34. Biswas S, Bryant RV, Travis S. Interfering with leukocyte trafficking in Crohn’s disease. Best Pract Res Clin Gastroenterol. 2019;(38–39):101617. doi: 10.1016/j.bpg.2019.05.004
  35. Berer K, Boziki M, Krishnamoorthy G. Selective accumulation of pro-inflammatory T cells in the intestine contributes to the resistance to autoimmune demyelinating disease. PLoS One. 2014;9(2):e87876. doi: 10.1371/journal.pone.0087876
  36. Kunisawa J, Kurashima Y, Higuchi M, et al. Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium. J Exp Med. 2007;204(10): 2335–2348. doi: 10.1084/jem.20062446
  37. Deguchi Y, Andoh A, Yagi Y, et al. The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice. Oncol Rep. 2006;16(4):699–703.
  38. Huang Y, Mao K, Chen X, et al. S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense. Science. 2018;359(6371):114–119. doi: 10.1126/science.aam5809
  39. Vidal-Martinez G, Vargas-Medrano J, Gil-Tommee C, et al. FTY720/Fingolimod reduces synucleinopathy and improves gut motility in A53T mice. J Biol Chem. 2016;291(39):20811–20821. doi: 10.1074/jbc.M116.744029
  40. Gohda M, Kunisawa J, Miura F, et al. Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer’s patches for intestinal IgA responses. J Immunol. 2008;180(8): 5335–5343. doi: 10.4049/jimmunol.180.8.5335
  41. Kunisawa J, Kurashima Y, Gohda M, et al. Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production. Blood. 2007;109(9): 3749–3756. doi: 10.1182/blood-2006-08-041582
  42. Coles AJ, Cohen JA, Fox EJ, et al. Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology. 2017; 89(11):1117–1126. doi: 10.1212/WNL.0000000000004354
  43. Havrdova E, Horakova D, Kovarova I. Alemtuzumab in the treatment of multiple sclerosis: Key clinical trial results and considerations for use. Ther Adv Neurol Disord. 2015;8(1): 31–45. doi: 10.1177/1756285614563522
  44. Holmoy T, Fevang B, Olsen DB, et al. Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis. BMC Res Notes. 2019;12(1):497. doi: 10.1186/s13104-019-4507-6
  45. Baker D, Giovannoni G, Schmierer K. Marked neutropenia: Significant but rare in people with multiple sclerosis after alemtuzumab treatment. Mult Scler Relat Disord. 2017;(18): 181–183. doi: 10.1016/j.msard.2017.09.028
  46. Qu L, Li Q, Jiang H, et al. Effect of anti-mouse CD52 monoclonal antibody on mouse intestinal intraepithelial lymphocytes. Transplantation. 2009;88(6):766–772. doi: 10.1097/TP.0b013e3181b47c61
  47. Li QR, Wang CY, Tang C, et al. Reciprocal interaction between intestinal microbiota and mucosal lymphocyte in cynomolgus monkeys after alemtuzumab treatment. Am J Transplant. 2013; 13(4):899–910. doi: 10.1111/ajt.12148

Copyright (c) 2024 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies