Current issue
Journal content
Articles in press
Archive
About the Journal
About the Polish Annals of Medicine
Editorial Board
Open Access policy
Abstracting & indexing
Affiliated institutions
Contact
Instructions
Peer review process
Guide for authors
Publication ethics
Ethics and Patient Consent
User License
Usage of third party materials
Disclaimer
Reviewers
Guide for reviewers
List of reviewers
Review Form
REVIEW PAPER
Gut microbiota modification as an option in multiple sclerosis management
| 1 | Department of Neurology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Poland |
| 2 | Department of Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Poland |
CORRESPONDING AUTHOR
Beata Zwiernik
Clinic of Neurology, Department of Neurology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-082 Olsztyn, Poland. Tel.: +48 669 722 079.
Clinic of Neurology, Department of Neurology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-082 Olsztyn, Poland. Tel.: +48 669 722 079.
Submission date: 2020-05-17
Final revision date: 2020-08-09
Acceptance date: 2020-08-09
Online publication date: 2020-11-16
Pol. Ann. Med. 2020;27(2):238–243
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Multiple sclerosis (MS) is caused by the abnormal activity of the immune system. It is believed that the pathological immune response may be initiated in the intestines, the area of the largest antigen presentation. This is where autoreactive T and B cells are activated, which constitutes the pathomechanism of this disease. In a healthy organism, normal gut microbiota mediates the balance between pro- and anti-inflammatory activity of the immune system.
Aim:
This paper aims at describing the healthy gut microbiota, its changes in MS patients, factors that influence its composition and therapeutic corrective possibilities.
Material and methods:
The paper is based on available medical literature.
Results and discussion:
It has been evidenced that in MS patients the gut microbiota is dominated by pro-inflammatory species. This may be caused by environmental factors, for instance, the diet, antibiotics or stimulants. Methods of the microbiota correction involve dietary change, prebiotics and probiotics as well as fecal microbiota transplantation (FMT). FMT is a particularly safe and promising method that has proven its efficiency on an animal model of MS.
Conclusions:
Experimental research has revealed that the correction of the gut microbiota may lead to MS remission or alleviation. FMT utilized in inflammatory bowel disease seems to be presently the most comprehensive intervention. Since only incidental reports of its efficiency in humans are presently available, further clinical studies are necessary.
Multiple sclerosis (MS) is caused by the abnormal activity of the immune system. It is believed that the pathological immune response may be initiated in the intestines, the area of the largest antigen presentation. This is where autoreactive T and B cells are activated, which constitutes the pathomechanism of this disease. In a healthy organism, normal gut microbiota mediates the balance between pro- and anti-inflammatory activity of the immune system.
Aim:
This paper aims at describing the healthy gut microbiota, its changes in MS patients, factors that influence its composition and therapeutic corrective possibilities.
Material and methods:
The paper is based on available medical literature.
Results and discussion:
It has been evidenced that in MS patients the gut microbiota is dominated by pro-inflammatory species. This may be caused by environmental factors, for instance, the diet, antibiotics or stimulants. Methods of the microbiota correction involve dietary change, prebiotics and probiotics as well as fecal microbiota transplantation (FMT). FMT is a particularly safe and promising method that has proven its efficiency on an animal model of MS.
Conclusions:
Experimental research has revealed that the correction of the gut microbiota may lead to MS remission or alleviation. FMT utilized in inflammatory bowel disease seems to be presently the most comprehensive intervention. Since only incidental reports of its efficiency in humans are presently available, further clinical studies are necessary.
FUNDING
University of Warmia and Mazury in Olsztyn institutional grant number 61.610.005-110.
CONFLICT OF INTEREST
None declared.
REFERENCES (62)
1.
Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010;162(1):1–11. https://doi.org/10.1111/j.1365....
2.
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545–558. https://doi.org/10.1038/nri387....
3.
Sospedra M, Martin R. Immunology of multiple sclerosis. Semin Neurol. 2016;36(2):115–127. https://doi.org/10.1055/s-0036....
4.
Kirby TO, Ochoa-Repáraz J. The gut microbiome in multiple sclerosis: A potential therapeutic avenue. Med Sci (Basel). 2018;6(3):69. https://doi.org/10.3390/medsci....
5.
Flannigan KL, Geem D, Harusato A, Denning TL. Intestinal antigen-presenting cells: Key regulators of immune homeostasis and inflammation. Am J Pathol. 2015;185(7):1809–1819. https://doi.org/10.1016/j.ajpa....
6.
Pröbstel AK, Baranzini SE. The role of the gut microbiome in multiple sclerosis risk and progression: Towards characterization of the ‘MS Microbiome’. Neurotherapeutics. 2018;15(1):126–134. https://doi.org/10.1007/s13311....
7.
Litvak Y, Byndloss MX, Bäumler AJ. Colonocyte metabolism shapes the gut microbiota. Science. 2018;362(6418): eaat9076. https://doi.org/10.1126/scienc....
8.
Holly MK, Smith JG. Paneth cells during viral infection and pathogenesis. Viruses. 2018;10(5):225. https://doi.org/10.3390/v10050....
9.
Flint HJ, Scott KP, Louis P, Duncan SH. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol. 2012;9(10):577–589. https://doi.org/10.1038/nrgast....
10.
Parada Venegas D, De la Fuente MK, Landskron G, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. 2019;10:277. Corrigendum in Front Immunol. 2019;10:1486. https://doi.org/10.3389/fimmu.....
11.
Chu F, Shi M, Lang Y, et al. Gut microbiota in multiple sclerosis and experimental autoimmune encephalomyelitis: Current application and future perspectives. Mediators Inflamm. 2018;2018:8168717. https://doi.org/10.1155/2018/8....
12.
Mueller DL. Mechanisms maintaining peripheral tolerance. Nat Immunol. 2010;11:21–27.
13.
Stagg AJ, Hart AL, Knight SC, Kamm MA. The dendritic cell: Its role in intestinal inflammation and relationship with gut bacteria. Gut. 2003;52(10):1522–1529. https://doi.org/10.1136/gut.52....
14.
Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28(2):203–209.
15.
Berer K, Gerdes LA, Cekanaviciute E, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. PNAS. 2017;114(40):10719–10724. https://doi.org/10.1073/pnas.1....
16.
Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904. https://doi.org/10.1152/physre....
17.
Gérard P. Gut microbiota and obesity. Cell Mol Life Sci. 2016;73(1):147–162. https://doi.org/10.1007/s00018....
18.
Freedman SN, Shahi SK, Mangalam AK. The “gut feeling”: Breaking down the role of the microbiome in multiple sclerosis. Neeurotherapeutics. 2018;15(1):109–125. https://doi.org/10.1007/s13311....
19.
Chen J, Chia N, Kalari KR, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Scie Reports. 2016;6(1):28484. https://doi.org/10.1038/srep28....
20.
Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple cclerosis, with striking depletion of species belonging to Clostridia XIva and IV Clusters. Plos One. 2015;10(9):e0137429. https://doi.org/10.1371/journa....
21.
Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. https://doi.org/10.1038/nature....
22.
Schepici G, Silvestro S, Bramanti P, Mazzon E. The gut microbiota in multiple sclerosis: An overview of clinical trials. Cell Transplant. 2019;28(12):1507–1527. https://dx.doi.org/10.1177%2F0....
23.
Cekanaviciute E, Yoo BB, Runia TF, et al. Gut bacteria from multiple sclerosis patients modulate human T cellee and exacerbate symptoms in mouse models. PNAS. 2017;114(40):10713–10718. https://doi.org/10.1073/pnas.1....
24.
Ochoa-Repáraz J, Mielcarz DW, Haque-Begum S, Kasper LH. Induction of a regulatory B cell population in experimental allergic encephalomyelitis by alternation of the gut commensal microflora. Gut Microbes. 2010;1(2):103–108. https://doi.org/10.4161/gmic.1....
25.
Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7(1):17–44. https://dx.doi.org/10.3390%2Fn....
26.
Fallani M, Amarri S, Uusijarvi A, et al. Determinants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centres. Microbiology (Reading). 2011;157(Pt 5):1385–1392. https://doi.org/10.1099/mic.0.....
27.
Kabat AM, Srinivasan N, Maloy KJ. Modulation of immune development and function by intestinal microbiota. Trends Immunol. 2014;35(11):507–517. https://doi.org/10.1016/j.it.2....
28.
Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–108. https://dx.doi.org/10.1126%2Fs....
29.
Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488:178–184. https://doi.org/10.1038/nature....
30.
Walker AW, Ince J, Duncan SH, et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 2011;5:220–230. https://doi.org/10.1038/ismej.....
31.
Opazo M, Ortega-Rocha EM, Coronado-Arrázola I, et al. Intestinal microbiota influences non-intestinal related autoimmune diseases. Front Microbiol. 2018;9:432. https://dx.doi.org/10.3389%2Ff....
32.
Liszt K, Zwielehner J, Handschur M, Hippe B, Thaler R, Haslberger AG. Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting. Ann Nutr Metab. 2009;54(4):253–257. https://doi.org/10.1159/000229....
33.
Manzel A, Muller DN, Hafler DA, Erdman SE, Linker RA, Kleinewietfeld M. Role of “Western diet” in inflammatory autoimmune diseases. Curr Allergy Asthma Rep. 2014;14(1):404. https://dx.doi.org/10.1007%2Fs....
34.
Sekirov I, Tam NM, Jogova M, et al. Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection. Infect Immun. 2008;76(10):4726–4736. https://doi.org/10.1128/iai.00....
35.
Lagier JC, Million M, Hugon P, Armougom F, Raoult D. Human gut microbiota: repertoire and variations. Front Cell Infect Microbiol. 2012;2:136. https://doi.org/10.3389/fcimb.....
36.
Jaquet M, Rochat I, Moulin J, Cavin C, Bibiloni R. Impact of coffee consumption on the gut microbiota: A human volunteer study. Int J Food Microbiol. 2009;130(2):117–121. https://doi.org/10.1016/j.ijfo....
37.
Qiu F, Liang CL, Liu H, et al. Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?. Oncotarget. 2017;8(1):268–284. https://doi.org/10.18632/oncot....
38.
Borody T, Khoruts A. Fecal microbiota transplantations and emerging applications. Nat Rev Gastroenterol Hepatol. 2011;9(2):88–96. https://doi.org/10.1038/nrgast....
39.
Jirillo E, Jirillo F, Magrone T. Healthy effects exerted by prebiotics, probiotics, and symbiotics with special reference to their impact on the immune system. Int J Vitam Nutr Res. 2012;82(3):200–208. https://doi.org/10.1024/0300-9....
40.
Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125(6):1401–1412. https://doi.org/10.1093/jn/125....
41.
Davani-Davari D, Negahdaripour M, Karimzadeh I, et al. Prebiotics: Definition, types, sources, mechanism and clinical applications. Foods. 2019;8(3):92. https://dx.doi.org/10.3390%2Ff....
42.
Joossens M, De Preter V, Ballet V, Verbeke K, Rutgeerts P, Vermeir S. Effect of oligofructose-enriched inulin (OF-IN) ona bacterial composition and disease activity of patients with Crohn’s disease: results from a double-blinded randomised controlled trial. Gut. 2012;61(6):958. https://doi.org/10.1136/gutjnl....
43.
Calvo-Barreiro L, Eixarch H, Montalban X, Espejo C. Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis. Autoimmun Rev. 2018;17(2):165–174. https://doi.org/10.1016/j.autr....
44.
Timmerman HM, Koning CJ, Mulder L, Rombouts FM, Beynen AC. Monostrain, multistrain and multispecies probiotics – A comparison of functionality and efficacy. Int J Food Microbiol. 2004;96(3):219–233. https://doi.org/10.1016/j.ijfo....
45.
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:e9009. https://doi.org/10.1371/journa....
46.
Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2017;36(5):1245–1249. https://doi.org/10.1016/j.clnu....
47.
Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015. https://doi.org/10.1038/ncomms....
48.
Castillo-Alvarez F, Perez-Matute P, Oteo JA, et al. The influence of interferon β-1b on gut microbiota composition in patients with multiple sclerosis. Neurologia. 2018;S0213-4853(18)30158-0. https://doi.org/10.1016/j.nrl.....
49.
Duscha A, Gisevius B, Hirschberg S, et al. Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism. Cell. 2020;180(6):1067–1080.e16. https://doi.org/10.1016/j.cell....
50.
IDSA. Fecal Microbiota Transplantation: Investigational New Drug Protocol; 2018. http://www.idsociety.org/publi.... Accessed: October 30, 2020.
51.
Smith EA, Duarte-Chavez R, Samia H, et al. Fecal microbiota transplantation: Safe, simple, and effective. Int J Acad Med. 2018;4(2):142–152. https://doi.org/10.4103/IJAM.I....
52.
Paramsothy S, Paramsothy R, Rubin DT, et al. Faecal microbiota transplantation for inflammatory bowel disease: A systematic review and meta-analysis. J Crohns Colitis. 2017;11(10):1180–1199. https://doi.org/10.1093/ecco-j....
53.
Kump P, Wurm P, Gröchenig HP, et al. The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis. Aliment Pharmacol Ther. 2018;47(1):67–77. https://doi.org/10.1111/apt.14....
54.
Borody T, Leis S, Campbell J, Torres M, Nowak A. Fecal microbiota transplantation (FMT) in multiple sclerosis (MS). Amer J Gastroenterol. 2011;106:352.
55.
Makkawi S, Camara-Lemarroy C, Metz L. Fecal micobiota transplantation associated with 10-years of stability in a patient with SMSP. Neurology. 2018;5(4):e459. https://dx.doi.org/10.1212%2FN....
56.
Kremenchutzky M. Fecal microbial transplantation in relapsing multiple sclerosis patients. http://clinicaltrials.gov/ct2/.... Accessed: October 30, 2020.
57.
Silverman M. Fecal Microbial Transplantation for Relapsing Multiple Sclerosis Patients - a Placebo-controlled, Double-blinded, Randomized Trial. https://clinicaltrials.gov/ct2.... Accessed: October 30, 2020.
58.
Gelfand J. Fecal Microbiota Transplantation (FMT) of FMP30 in Relapsing-Remitting Multiple Sclerosis: A Phase 1b Clinical Trial to Evaluate Feasibility, Safety, Tolerability and Effects on Immune Function. https://www.clinicaltrials.gov.... Accessed: October 30, 2020.
59.
Afanasyev B. Allogeneic Fecal Microbiota Transplantation as a Consolidation Treatment After Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Sclerosis. https://www.clinicaltrials.gov....
60.
Keshavarzian A. Fecal Microbiota Transplantation (FMT) in Multiple Sclerosis. https://www.clinicaltrials.gov.... Accessed: October 30, 2020.
61.
Ng S. Safety and Efficacy of Fecal Microbiota Transplantation. https://www.clinicaltrials.gov.... Accessed: October 30, 2020.
62.
Guarnaccia J, Browne F. Oral FMT (Fecal Microbial Transplant) in Subjects With Multiple Sclerosis. https://www.clinicaltrials.gov.... Accessed: October 30, 2020.
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.