In search of the sources – the role of gut flora in health and disease. Part II – gut microbiota and multiple sclerosis Review article
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Published:
Dec 31, 2015
Keywords:
gut microbiota, multiple sclerosis, autoimmunity, fecal microbiota transplantation, gut colonization
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Abstract
Due to technological achievements and expanding knowledge, research on the world of microorganisms inhabiting our gastrointestinal tract has accelerated. We begin to understand the micro-universe of symbionts and commensals co-existing in our body. The biggest habitat for them in the human organism are the intestines, containing even 2 kg of intestinal flora. The spatial and molecular interactions of intestinal microorganisms influence not only their mutual communication and rivalry for survival, but also constitute a huge source of antigens, immunologically active compounds, hormones or neurotransmitters forming close links with the host. Intestinal microbiota plays a key role in the development of the immune system, and, in the light of current research, also nervous system. At the junction of theses two systems, there appear autoimmune disorders of the central nervous system, including multiple sclerosis. Despite a lot of research on the pathogenesis of this disease, the molecular background and a direct cause of its development remain unclear. Recent studies using advanced genetic and molecular methods show that the common denominator of the previous considerations may be the intestinal microbiota, both in terms of its evolutionarily conserved structure and composition as well as mutual communication between the microbiota and the host. This article discusses the role of the gut microbiome in the maintenance of immune homeostasis, the gut flora interaction with the immune, nervous and endocrine systems pointing at potential sources of autoimmunity and their role in the pathogenesis of multiple sclerosis, which may have therapeutical potential.
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References
1. Basak G.W.: W poszukiwaniu źródeł – rola flory jelitowej w zdrowiu i chorobie. Część I. MS Report 2015; 3(14): 15-18.
2. Backhed F., Ley R.E., Sonnenburg J.L. et al.: Host-bacterial mutualism in the human intestine. Science 2005; 307: 1915-1920.
3. Wang Y., Kasper L.H.: The role of microbiome in central nervous system disorders. Brain Behav. Immun. 2014; 38: 1-12.
4. Joscelyn J., Kasper L.H.: Digesting the emerging role for the gut microbiome in central nervous system demyelination. Mult. Scler. 2014; 20(12): 1553-1559.
5. Strachan D.P.: Family size, infection and atopy: the first decade of the ‘hygiene hypothesis’. Thorax 2000; 55: S2-10.
6. Bhargava P., Mowry E.M.: Gut microbiome and multiple sclerosis. Curr. Neurol. Neurosci. Rep. 2014; 14: 492.
7. Mielcarz D.W., Kasper L.H.: The gut microbiome in multiple sclerosis. Curr. Treat. Options Neurol. 2015; 17(4): 344.
8. Compston A., Coles A.: Multiple sclerosis. Lancet 2008; 372: 1502-1517.
9. Ochoa-Repáraz J., Kasper L.H.: Gut microbiome and the risk factors in central nervous system autoimmunity. FEBS Lett. 2014; 588(22): 4214-4222.
10. Fazekas F., Enzinger C., Wallner-Blazek M. et al.: Gender differences in MRI studies on multiple sclerosis. J. Neurol. Sci. 2009; 286: 28-30.
11. Trojano M., Lucchese G., Graziano G. et al.: Geographical variations in sex ratio trends over time in multiple sclerosis. PLoS One 2012; 7: e48078.
12. Maranduba C.M., De Castro S.B., de Souza G.T. et al.: Intestinal Microbiota as Modulators of the Immune System and Neuroimmune System: Impact on the Host Health and Homeostasis. J. Immunol. Res. 2015; 2015: 931574.
13. Maynard C.L., Elson C.O., Hatton R.D. et al.: Reciprocal interactions of the intestinal microbiota and immune system. Nature 2012; 489(7415): 231-224.
14. Goto Y., Ivanov I.I.: Intestinal epithelial cells as mediators of the commensal-host immune crosstalk. Immunol. Cell Biol. 2013; 91(3): 204-214.
15. Collins S.M., Surette M., Bercik P.: The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 2012; 10(11): 735-742.
16. Hooper L.V., Littman D.R., Macpherson A.J.: Interactions between the microbiota and the immune system. Science 2012; 336: 1268-1273.
17. Kamada N., Seo S., Chen G. et al.: Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 2013; 13(5): 321-335.
18. Macpherson A.J., Harris N.L.: Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 2004; 4: 478-485.
19. Round J.L., Mazmanian S.K.: Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl. Acad. of Sci. USA. 2010; 107: 12204-12209.
20. Furusawa Y., Obata Y., Fukuda S. et al.: Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013; 504(7480): 446-450.
21. Cryan J.F., Dinan T.G.: Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 2012; 13(10): 701-712.
22. Romijn J.A., Corssmit E.P., Havekes L.M. et al.: Gut-brain axis. Curr. Opin. Clin. Nutr. Metab. Care 2008; 11: 518-521.
23. Barrett E., Ross R.P., O’Toole P.W. et al.: γ-Aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 2012; 113: 411-417.
24. Rhee S.H., Pothoulakis C., Mayer E.A.: Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol. 2009; 6: 306-314.
25. Brun P., Giron M.C., Qesari M. et al.: Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 2013; 145(6): 1323-1333.
26. Barajon I., Serrao G., Arnaboldi F. et al.: Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J. Histochem. Cytochem. 2009; 57: 1013-1023.
27. Keast J.R., Furness J.B., Costa M.: Somatostatin in human enteric nerves. Distribution and characterization. Cell Tissue Res. 1984; 237(2): 299-308.
28. Ekblad E., Winther C., Ekman R. et al.: Projections of peptide-containing neurons in rat small intestine. Neuroscience 1987; 20(1): 169-188.
29. Kunze W.A., Mao Y.K., Wang B. et al.: Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J. Cell Mol. Med. 2009; 13(8 B): 2261-2270.
30. Rousseaux C., Thuru X., Gelot A. et al.: Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat. Med. 2007; 13(1): 35-37.
31. Sudo N., Chida Y., Aiba Y. et al.: Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 2004; 558(1): 263-275.
32. Sudo N.: Role of microbiome in regulating the HPA axis and its relevance to allergy. Chem. Immunol. Allergy. 2012; 98: 163-175.
33. Velickovic K., Markelic M., Golic I. et al.: Long-term dietary L-arginine supplementation increases endothelial nitric oxide synthase and vasoactive intestinal peptide immunoexpression in rat small intestine. Eur. J. Nutr. 2014; 53(3): 813-821.
34. Gonzalez-Rey E., Fernandez-Martin A., Chorny A. et al.: Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis: down-regulation of inflammatory and autoimmune responses. Am. J. Pathol. 2006; 168: 1179-1188.
35. Gonzalez D.A., Diaz B.B., Rodriguez Perez Mdel C. et al.: Sex hormones and autoimmunity. Immunol. Lett. 2010; 133(1): 6-13.
36. Klein S.L., Jedlicka A., Pekosz A.: The Xs and Y of immune responses to viral vaccines. Lancet Infect. Dis. 2010; 10: 338-349.
37. Chervonsky A.V.: Influence of microbial environment on autoimmunity. Nat. Immunol. 2010; 11: 28-35.
38. Gomez A., Luckey D., Taneja V.: The gut microbiome in autoimmunity: Sex matters. Clin. Immunol. 2015; 159(2): 154-162.
39. Ridlon J.M., Ikegawa S., Alves J.M. et al.: Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens. J. Lipid Res. 2013; 54: 2437-2449.
40. Yurkovetskiy L., Burrows M., Khan A.A. et al.: Gender bias in autoimmunity is influenced by microbiota. Immunity 2013; 39: 400-412.
41. Markle J.G., Frank D.N., Mortin-Toth S. et al.: Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 2013; 339: 1084-1088.
42. Mangalam A.K., Taneja V., David C.S.: HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile. J. Immunol. 2013; 190(2): 513-518.
43. Ochoa-Repáraz J., Riccardi C., Rynda A. et al.: Regulatory T cell vaccination without autoantigen protects against experimental autoimmune encephalomyelitis. J. Immunol. 2007; 178: 1791-1799.
44. Ochoa-Repáraz J., Mielcarz D.W., Ditrio L.E. et al.: Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J. Immunol. 2009; 183: 6041-6050.
45. Ochoa-Repáraz J., Mielcarz D.W., Ditrio L.E. et al.: Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J. Immunol. 2010; 185: 4101-4108.
46. Ochoa-Repáraz J., Mielcarz D.W., Wang Y. et al.: A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010; 3: 487-495.
47. Ochoa-Repáraz J., Mielcarz D.W., Haque-Begum S. et al.: Induction of a regulatory B cell population in experimental allergic encephalomyelitis by alteration of the gut commensal microflora. Gut Microbes 2010; 1: 103-108.
48. Begum-Haque S., Christy M., Ochoa-Repáraz J. et al.: Augmentation of regulatory B cell activity in experimental allergic encephalomyelitis by glatiramer acetate. J. Neuroimmunol. 2011; 232: 136-144.
49. Yokote H., Miyake S., Croxford J.L. et al.: NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora. Am. J. Pathol. 2008; 173: 1714-1723.
50. Lee Y.K., Menezes J.S., Umesaki Y. et al.: Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA. 2011; 108(supl.): 4615-4622.
51. Davis C.P., Savage D.C.: Habitat, succession, attachment, and morphology of segmented, filamentous microbes indigenous to the murine gastrointestinal tract. Infect. Immun. 1974; 10: 948-956.
52. Westall F.C.: Molecular mimicry revisited: gut bacteria and multiple sclerosis. J. Clin. Microbiol. 2006; 44: 2099-2104.
53. 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.
54. Takata K., Kinoshita M., Okuno T. et al.: The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells. PLoS ONE 2011; 6: e27644.
55. Maassen C.B., Claassen E.: Strain-dependent effects of probiotic lactobacilli on EAE autoimmunity. Vaccine 2008; 26: 2056-2057.
56. Kwon H.K., Kim G.C., Kim Y. et al.: Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin. Immunol. 2013; 146: 217-227.
57. Mowry E., Waubant E., Chehoud C. et al.: Gut bacterial populations in multiple sclerosis and in health. Neurology 2012; 78: P05.106.
58. Jhangi S., Roopali G., Bonnie G. et al.: Increased Archaea species and changes with therapy in gut microbiome of multiple sclerosis subjects. Neurology 2014; 82: S24.001.
59. Tremlett H., Douglas F., Susan L. et al.: Gut microbiome in early pediatric multiple sclerosis: a case-control study. Neurology 2015; 84: P4.027.
60. Rumah K.R., Linden J., Fischetti V.A. et al.: 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: e76359.
61. Saemann M.D., Bohmig G.A., Osterreicher C.H. et al.: Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. FASEB J. 2000; 14: 2380-2382.
62. 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.
63. Atarashi K., Tanoue T., Shima T. et al.: Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011; 331: 337-341.
64. Atarashi K., Tanoue T., Oshima K. et al.: Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013; 500: 232-236.
65. Galland L.: The gut microbiome and the brain. J. Med. Food 2014; 17(12): 1261-1272.
2. Backhed F., Ley R.E., Sonnenburg J.L. et al.: Host-bacterial mutualism in the human intestine. Science 2005; 307: 1915-1920.
3. Wang Y., Kasper L.H.: The role of microbiome in central nervous system disorders. Brain Behav. Immun. 2014; 38: 1-12.
4. Joscelyn J., Kasper L.H.: Digesting the emerging role for the gut microbiome in central nervous system demyelination. Mult. Scler. 2014; 20(12): 1553-1559.
5. Strachan D.P.: Family size, infection and atopy: the first decade of the ‘hygiene hypothesis’. Thorax 2000; 55: S2-10.
6. Bhargava P., Mowry E.M.: Gut microbiome and multiple sclerosis. Curr. Neurol. Neurosci. Rep. 2014; 14: 492.
7. Mielcarz D.W., Kasper L.H.: The gut microbiome in multiple sclerosis. Curr. Treat. Options Neurol. 2015; 17(4): 344.
8. Compston A., Coles A.: Multiple sclerosis. Lancet 2008; 372: 1502-1517.
9. Ochoa-Repáraz J., Kasper L.H.: Gut microbiome and the risk factors in central nervous system autoimmunity. FEBS Lett. 2014; 588(22): 4214-4222.
10. Fazekas F., Enzinger C., Wallner-Blazek M. et al.: Gender differences in MRI studies on multiple sclerosis. J. Neurol. Sci. 2009; 286: 28-30.
11. Trojano M., Lucchese G., Graziano G. et al.: Geographical variations in sex ratio trends over time in multiple sclerosis. PLoS One 2012; 7: e48078.
12. Maranduba C.M., De Castro S.B., de Souza G.T. et al.: Intestinal Microbiota as Modulators of the Immune System and Neuroimmune System: Impact on the Host Health and Homeostasis. J. Immunol. Res. 2015; 2015: 931574.
13. Maynard C.L., Elson C.O., Hatton R.D. et al.: Reciprocal interactions of the intestinal microbiota and immune system. Nature 2012; 489(7415): 231-224.
14. Goto Y., Ivanov I.I.: Intestinal epithelial cells as mediators of the commensal-host immune crosstalk. Immunol. Cell Biol. 2013; 91(3): 204-214.
15. Collins S.M., Surette M., Bercik P.: The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 2012; 10(11): 735-742.
16. Hooper L.V., Littman D.R., Macpherson A.J.: Interactions between the microbiota and the immune system. Science 2012; 336: 1268-1273.
17. Kamada N., Seo S., Chen G. et al.: Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 2013; 13(5): 321-335.
18. Macpherson A.J., Harris N.L.: Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 2004; 4: 478-485.
19. Round J.L., Mazmanian S.K.: Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl. Acad. of Sci. USA. 2010; 107: 12204-12209.
20. Furusawa Y., Obata Y., Fukuda S. et al.: Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013; 504(7480): 446-450.
21. Cryan J.F., Dinan T.G.: Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 2012; 13(10): 701-712.
22. Romijn J.A., Corssmit E.P., Havekes L.M. et al.: Gut-brain axis. Curr. Opin. Clin. Nutr. Metab. Care 2008; 11: 518-521.
23. Barrett E., Ross R.P., O’Toole P.W. et al.: γ-Aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 2012; 113: 411-417.
24. Rhee S.H., Pothoulakis C., Mayer E.A.: Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol. 2009; 6: 306-314.
25. Brun P., Giron M.C., Qesari M. et al.: Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 2013; 145(6): 1323-1333.
26. Barajon I., Serrao G., Arnaboldi F. et al.: Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J. Histochem. Cytochem. 2009; 57: 1013-1023.
27. Keast J.R., Furness J.B., Costa M.: Somatostatin in human enteric nerves. Distribution and characterization. Cell Tissue Res. 1984; 237(2): 299-308.
28. Ekblad E., Winther C., Ekman R. et al.: Projections of peptide-containing neurons in rat small intestine. Neuroscience 1987; 20(1): 169-188.
29. Kunze W.A., Mao Y.K., Wang B. et al.: Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J. Cell Mol. Med. 2009; 13(8 B): 2261-2270.
30. Rousseaux C., Thuru X., Gelot A. et al.: Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat. Med. 2007; 13(1): 35-37.
31. Sudo N., Chida Y., Aiba Y. et al.: Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 2004; 558(1): 263-275.
32. Sudo N.: Role of microbiome in regulating the HPA axis and its relevance to allergy. Chem. Immunol. Allergy. 2012; 98: 163-175.
33. Velickovic K., Markelic M., Golic I. et al.: Long-term dietary L-arginine supplementation increases endothelial nitric oxide synthase and vasoactive intestinal peptide immunoexpression in rat small intestine. Eur. J. Nutr. 2014; 53(3): 813-821.
34. Gonzalez-Rey E., Fernandez-Martin A., Chorny A. et al.: Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis: down-regulation of inflammatory and autoimmune responses. Am. J. Pathol. 2006; 168: 1179-1188.
35. Gonzalez D.A., Diaz B.B., Rodriguez Perez Mdel C. et al.: Sex hormones and autoimmunity. Immunol. Lett. 2010; 133(1): 6-13.
36. Klein S.L., Jedlicka A., Pekosz A.: The Xs and Y of immune responses to viral vaccines. Lancet Infect. Dis. 2010; 10: 338-349.
37. Chervonsky A.V.: Influence of microbial environment on autoimmunity. Nat. Immunol. 2010; 11: 28-35.
38. Gomez A., Luckey D., Taneja V.: The gut microbiome in autoimmunity: Sex matters. Clin. Immunol. 2015; 159(2): 154-162.
39. Ridlon J.M., Ikegawa S., Alves J.M. et al.: Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens. J. Lipid Res. 2013; 54: 2437-2449.
40. Yurkovetskiy L., Burrows M., Khan A.A. et al.: Gender bias in autoimmunity is influenced by microbiota. Immunity 2013; 39: 400-412.
41. Markle J.G., Frank D.N., Mortin-Toth S. et al.: Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science 2013; 339: 1084-1088.
42. Mangalam A.K., Taneja V., David C.S.: HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile. J. Immunol. 2013; 190(2): 513-518.
43. Ochoa-Repáraz J., Riccardi C., Rynda A. et al.: Regulatory T cell vaccination without autoantigen protects against experimental autoimmune encephalomyelitis. J. Immunol. 2007; 178: 1791-1799.
44. Ochoa-Repáraz J., Mielcarz D.W., Ditrio L.E. et al.: Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J. Immunol. 2009; 183: 6041-6050.
45. Ochoa-Repáraz J., Mielcarz D.W., Ditrio L.E. et al.: Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J. Immunol. 2010; 185: 4101-4108.
46. Ochoa-Repáraz J., Mielcarz D.W., Wang Y. et al.: A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010; 3: 487-495.
47. Ochoa-Repáraz J., Mielcarz D.W., Haque-Begum S. et al.: Induction of a regulatory B cell population in experimental allergic encephalomyelitis by alteration of the gut commensal microflora. Gut Microbes 2010; 1: 103-108.
48. Begum-Haque S., Christy M., Ochoa-Repáraz J. et al.: Augmentation of regulatory B cell activity in experimental allergic encephalomyelitis by glatiramer acetate. J. Neuroimmunol. 2011; 232: 136-144.
49. Yokote H., Miyake S., Croxford J.L. et al.: NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora. Am. J. Pathol. 2008; 173: 1714-1723.
50. Lee Y.K., Menezes J.S., Umesaki Y. et al.: Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA. 2011; 108(supl.): 4615-4622.
51. Davis C.P., Savage D.C.: Habitat, succession, attachment, and morphology of segmented, filamentous microbes indigenous to the murine gastrointestinal tract. Infect. Immun. 1974; 10: 948-956.
52. Westall F.C.: Molecular mimicry revisited: gut bacteria and multiple sclerosis. J. Clin. Microbiol. 2006; 44: 2099-2104.
53. 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.
54. Takata K., Kinoshita M., Okuno T. et al.: The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells. PLoS ONE 2011; 6: e27644.
55. Maassen C.B., Claassen E.: Strain-dependent effects of probiotic lactobacilli on EAE autoimmunity. Vaccine 2008; 26: 2056-2057.
56. Kwon H.K., Kim G.C., Kim Y. et al.: Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin. Immunol. 2013; 146: 217-227.
57. Mowry E., Waubant E., Chehoud C. et al.: Gut bacterial populations in multiple sclerosis and in health. Neurology 2012; 78: P05.106.
58. Jhangi S., Roopali G., Bonnie G. et al.: Increased Archaea species and changes with therapy in gut microbiome of multiple sclerosis subjects. Neurology 2014; 82: S24.001.
59. Tremlett H., Douglas F., Susan L. et al.: Gut microbiome in early pediatric multiple sclerosis: a case-control study. Neurology 2015; 84: P4.027.
60. Rumah K.R., Linden J., Fischetti V.A. et al.: 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: e76359.
61. Saemann M.D., Bohmig G.A., Osterreicher C.H. et al.: Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. FASEB J. 2000; 14: 2380-2382.
62. 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.
63. Atarashi K., Tanoue T., Shima T. et al.: Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011; 331: 337-341.
64. Atarashi K., Tanoue T., Oshima K. et al.: Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013; 500: 232-236.
65. Galland L.: The gut microbiome and the brain. J. Med. Food 2014; 17(12): 1261-1272.