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Fecal Microbiota Transplantation in the Treatment-Resistant Psychiatric Disorders

  • Alper Evrensel
  • Mehmet Emin Ceylan
Chapter

Abstract

A large number of evidence have been obtained regarding the relationship between gut microbiota and the brain during the last decade. Absence of gut microbiota or changes in the bacterial composition can cause significant results in body and brain functions. Aging, stress, nutrition, and medications like antibiotics may change the intestinal microbiota bacterial composition. This condition, called dysbiosis, can be repaired through probiotics or fecal microbiota transplantation (FMT). According to the historical records, FMT was first applied in the fourth century. Having been forgotten for centuries, this treatment method has been again put into practice in the twentieth century. It is effective in the treatment of recurrent Clostridium difficile infection and inflammatory bowel diseases (Crohn’s disease and ulcerative colitis). We have limited information regarding its application in psychiatric disorders. However, clinical and preclinical studies carried out on the gut-brain connection are promising.

Keywords

Fecal microbiota transplantation Microbiome Psychiatry Immune system Gut-brain axis Treatment resistance 

References

  1. 1.
    Rieder R, Wisniewski PJ, Alderman BL, Campbell SC. Microbes and mental health: a review. Brain Behav Immun. 2017;66:9–17.CrossRefGoogle Scholar
  2. 2.
    Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1–9.CrossRefGoogle Scholar
  3. 3.
    Khanna S, Tosh PK. A clinican’s primer on the role of the microbiome in human health and disease. Mayo Clin Proc. 2014;89(1):107–14.CrossRefGoogle Scholar
  4. 4.
    Branton WG, Ellestad KK, Maingat F, Wheatley BM, Rud E, Warren RL, et al. Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status. PLoS One. 2013;8(1):e54673.CrossRefGoogle Scholar
  5. 5.
    Evrensel A, Ceylan ME. The gut-brain axis: the missing link in depression. Clin Psychopharmacol Neurosci. 2015;13(3):239–44.CrossRefGoogle Scholar
  6. 6.
    Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533.CrossRefGoogle Scholar
  7. 7.
    Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–30.CrossRefGoogle Scholar
  8. 8.
    Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The central nervous system and the gut microbiome. Cell. 2016;167(4):915–32.CrossRefGoogle Scholar
  9. 9.
    Evrensel A, Ceylan ME. Microbiome: the missing link in neuropsychiatric disorders. Eur Med J Innov. 2017;1(1):83–8.Google Scholar
  10. 10.
    Xu MQ, Cao HL, Wang WQ, Wang S, Cao XC, Yan F, et al. Fecal microbiota transplantation broadening its application beyond intestinal disorders. World J Gastroenterol. 2015;21(1):102–11.CrossRefGoogle Scholar
  11. 11.
    Scott KA, Ida M, Peterson VL, Prenderville JA, Moloney GM, Izumo T, et al. Revisiting Metchnikoff: age-related alterations in microbiota-gut-brain axis in the mouse. Brain Behav Immun. 2017;65:20–32.CrossRefGoogle Scholar
  12. 12.
    Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PW. Psychobiotics and the manipulation of Bacteria-gut-brain signals. Trends Neurosci. 2016;39(11):763–81.CrossRefGoogle Scholar
  13. 13.
    Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336(6080):489–93.CrossRefGoogle Scholar
  14. 14.
    McCusker RH, Kelley KW. Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol. 2013;216(Pt 1):84–98.CrossRefGoogle Scholar
  15. 15.
    McKernan DP, Dennison U, Gaszner G, Cryan JF, Dinan TG. Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype. Transl Psychiatry. 2011;1:e36.CrossRefGoogle Scholar
  16. 16.
    Dinan TG, Quigley EM. Probiotics in the treatment of depression: science or science fiction? Aust New Zeland J Psychiatry. 2011;45(12):1023–5.CrossRefGoogle Scholar
  17. 17.
    Carvalho FA, Aitken JD, Vijay-Kumar M, Gewirtz AT. Toll-like receptor-gut microbiota interactions: perturb at your own risk. Annu Rev Physiol. 2012;74:177–98.CrossRefGoogle Scholar
  18. 18.
    Lucas K, Maes M. Role of the toll like receptor (TLR) radical cyclein chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013;48(1):190–204.CrossRefGoogle Scholar
  19. 19.
    Ait-Belgnaoui A, Durand H, Cartier C, Chaumaz G, Eutamene H, Ferrier L, et al. Prevention of gut leakiness by intestinal microbiota modulation leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012;37(11):1885–95.CrossRefGoogle Scholar
  20. 20.
    Jeon SW, Kim YK. Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? World J Psychiatry. 2016;6(3):283–93.CrossRefGoogle Scholar
  21. 21.
    Kim YK, Na KS, Myint AM, Leonard BE. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;64:277–84.CrossRefGoogle Scholar
  22. 22.
    Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, et al. Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry. 2012;73(2):1128–38.CrossRefGoogle Scholar
  23. 23.
    McNutt MD, Liu S, Manatunga A, Royster EB, Raison CL, Woolwine BJ, et al. Neurobehavioral effects of interferon-α in patients with hepatitis-C: symptom dimensions and responsiveness to paroxetine. Neuropsychopharmacology. 2012;37(6):1444–54.CrossRefGoogle Scholar
  24. 24.
    Maes M, Kenis G, Kubera M, De Baets M, Steinbusch H, Bosmans E. The negative immunoregulatory effects of fluoxetine in relation to the cAMP-dependent PKA pathway. Int Immunopharmacol. 2005;5(3):609–18.CrossRefGoogle Scholar
  25. 25.
    Levkovich T, Poutahidis T, Smillie C, Varian BJ, Ibrahim YM, Lakritz JR, et al. Probiotic bacteria induce a ‘glow of health’. PLoS One. 2013;8(1):e53867.CrossRefGoogle Scholar
  26. 26.
    Kopp MV, Goldstein M, Dietschek A, Sofke J, Heinzmann A, Urbanek R. Lactobacillus GG has in vitro effects on enhanced interleukin-10 and interferon-gamma release of mononuclear cells but no in vivo effects in supplemented mothers and their neonates. Clin Exp Allergy. 2008;38(4):602–10.CrossRefGoogle Scholar
  27. 27.
    Costello EK, Stagaman K, Dethlefsen L, Bohannan J, Relman DA. The application of ecological theory toward an understanding of the human microbiome. Science. 2012;336(6086):1255–62.CrossRefGoogle Scholar
  28. 28.
    Smythies LE, Smythies JR. Microbiota, the immune system, black moods and the brain melancholia updated. Front Hum Neurosci. 2014;8:720.CrossRefGoogle Scholar
  29. 29.
    Helander HF, Fändriks L. Surface area of the digestive tract – revisited. Scand J Gastroenterol. 2014;49(6):681–9.CrossRefGoogle Scholar
  30. 30.
    Borre YE, O’keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014;20(9):509–18.CrossRefGoogle Scholar
  31. 31.
    Maes M, Kubera M, Leunis JC, Berk M. Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord. 2012;141(1):55–62.CrossRefGoogle Scholar
  32. 32.
    Fink MP. Leaky gut hypothesis: a historical perspective. Crit Care Med. 1990;18(5):579–80.CrossRefGoogle Scholar
  33. 33.
    Hornig M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol. 2013;25(5):488–95.CrossRefGoogle Scholar
  34. 34.
    Fetissov SO, Déchelotte P. The new link between gut–brain axis and neuropsychiatric disorders. Curr Opin Clin Nutr Metab Care. 2011;14(5):477–82.CrossRefGoogle Scholar
  35. 35.
    Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016;22(3):250–3.CrossRefGoogle Scholar
  36. 36.
    Bäckhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17(5):690–703.CrossRefGoogle Scholar
  37. 37.
    Bager P, Wohlfahrt J, Westergaard T. Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clin Exp Allergy. 2008;38(4):634–42.CrossRefGoogle Scholar
  38. 38.
    Slykerman RF, Thompson J, Waldie KE, Murphy R, Wall C, Mitchell EA. Antibiotics in the first year of life and subsequent neurocognitive outcomes. Acta Paediatr. 2017;106(1):87–94.CrossRefGoogle Scholar
  39. 39.
    Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141(2):599–609.CrossRefGoogle Scholar
  40. 40.
    Desbonnet L, Clarke G, Traplin A, O’Sullivan O, Crispie F, Moloney RD, et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behavior. Brain Behav Immun. 2015;48:165–73.CrossRefGoogle Scholar
  41. 41.
    Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011;23(3):255–64.CrossRefGoogle Scholar
  42. 42.
    Hoban AE, Stilling RM, Moloney G, Shanahan F, Dinan TG, Clarke G, et al. The microbiome regulates amygdala-dependent fear recall. Mol Psychiatry. 2017;23(5):1134–44.CrossRefGoogle Scholar
  43. 43.
    Macedo D, Filho AJMC, Soares de Sousa CN, Quevedo J, Barichello T, Júnior HVN, et al. Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness. J Affect Disord. 2017;208:22–32.CrossRefGoogle Scholar
  44. 44.
    Evrensel A, Ceylan ME. The role of fecal microbiota transplantation in psychiatric treatment. Anadolu Psikiyatri Derg. 2015;16(5):380.Google Scholar
  45. 45.
    Evrensel A, Ceylan ME. Fecal microbiota transplantation and its usage in neuropsychiatric disorders. Clin Psychopharmacol Neurosci. 2016;14(3):231–7.CrossRefGoogle Scholar
  46. 46.
    Vindigni SM, Surawicz CM. Fecal microbiota transplantation. Gastroenterol Clin N Am. 2017;46(1):171–85.CrossRefGoogle Scholar
  47. 47.
    Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-old fecal microbiota transplantation? Am J Gastroenterol. 2012;107(11):1755.CrossRefGoogle Scholar
  48. 48.
    Jia NA. Misleading reference for fecal microbiota transplant. Am J Gastroenterol. 2015;110(12):1731.CrossRefGoogle Scholar
  49. 49.
    Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S. Bacteriotherapy using fecal flora: toying with human motions. J Clin Gastroenterol. 2004;38(6):475–83.CrossRefGoogle Scholar
  50. 50.
    Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013;145(5):946–53.CrossRefGoogle Scholar
  51. 51.
    Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854–9.PubMedGoogle Scholar
  52. 52.
    Bowden TA, Mansberger AR, Lykins LE. Pseudomembranous enterocolitis: mechanism of restoring floral homeostasis. Am Surg. 1981;47(4):178–83.PubMedGoogle Scholar
  53. 53.
    Brandt LJ, Aroniadis OC, Mellow M, Kanatzar A, Kelly C, Park T, et al. Long-term follow-up of colonoscopic fecal microbiota transplantation for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(7):1079–87.CrossRefGoogle Scholar
  54. 54.
    Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry. 2016;21(6):786–96.CrossRefGoogle Scholar
  55. 55.
    Ma Y, Liu J, Rhodes C, Nie Y, Zhang F. Ethical issues in fecal microbiota transplantation in practice. Am J Bioeth. 2017;17:34–45.CrossRefGoogle Scholar
  56. 56.
    Di Bella S, Drapeau C, García-Almodóvar E, Petrosillo N. Fecal microbiota transplantation: the state of the art. Infect Dis Rep. 2013;5(2):e13.CrossRefGoogle Scholar
  57. 57.
    Evrensel A, Ceylan ME. The future of fecal microbiota transplantation method in neuropsychiatric disorders. Turk Psikiyatri Dergisi. 2016;27(1):71–2.PubMedGoogle Scholar
  58. 58.
    Aroniadis OC, Brandt LJ. Fecal microbiota transplantation: past, present and future. Curr Opin Gastroenterol. 2013;29(1):79–84.CrossRefGoogle Scholar
  59. 59.
    Brandt LJ, Aroniadis OC. An overview of fecal microbiota transplantation: techniques, indications, and outcomes. Gastrointest Endosc. 2013;78(2):240–9.CrossRefGoogle Scholar
  60. 60.
    Youngster I, Gerding DN. Editorial: making fecal microbiota transplantation easier to swallow: freeze-dried preparation for recurrent Clostridium difficile infections. Am J Gastroenterol. 2017;112(6):948–50.CrossRefGoogle Scholar
  61. 61.
    Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014;312(17):1772–8.CrossRefGoogle Scholar
  62. 62.
    Borody TJ, Brandt LJ, Paramsothy S. Therapeutic faecal microbiota transplantation: current status and future developments. Curr Opin Gastroenterol. 2014;30(1):97–105.CrossRefGoogle Scholar
  63. 63.
    Bakken JS, Borody T, Brandt LJ, Brill JV, Demarco DC, Franzos MA, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9(12):1044–9.CrossRefGoogle Scholar
  64. 64.
    Kubera M, Curzytek K, Duda W, Leskiewicz M, Basta-Kaim A, Budziszewska B, et al. A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months. Brain Behav Immun. 2013;31:96–104.CrossRefGoogle Scholar
  65. 65.
    Macpherson AJ, Uhr T. Gut flora-mechanisms of regulation. Eur J Surg Suppl. 2002;587:3–7.Google Scholar
  66. 66.
    Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170(4):1179–88.CrossRefGoogle Scholar
  67. 67.
    Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105(5):755–64.CrossRefGoogle Scholar
  68. 68.
    Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011;2(4):256–61.CrossRefGoogle Scholar
  69. 69.
    Bruce-Keller AJ, Salbaum JM, Luo M, Blanchard E 4th, Taylor CM, Welsh DA, et al. Obese-type gut microbionta induced neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77(7):607–15.CrossRefGoogle Scholar
  70. 70.
    Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451–63.CrossRefGoogle Scholar
  71. 71.
    Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002;35(Suppl 1):6–16.CrossRefGoogle Scholar
  72. 72.
    Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol. 2004;70(11):6459–65.CrossRefGoogle Scholar
  73. 73.
    Schwarz E, Maukonen J, Hyytiäinen T, Kieseppä T, Orešič M, Sabunciyan S, et al. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophr Res. 2017;192:398–403.CrossRefGoogle Scholar
  74. 74.
    Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186–94.CrossRefGoogle Scholar
  75. 75.
    Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann General Psychiatry. 2017;16:14.CrossRefGoogle Scholar
  76. 76.
    Noble EE, Hsu TM, Kanoski SE. Gut to brain Dysbiosis: mechanisms linking western diet consumption, the microbiome, and cognitive impairment. Front Behav Neurosci. 2017;11:9.CrossRefGoogle Scholar
  77. 77.
    Allen AP, Hutch W, Borre YE, Kennedy PJ, Temko A, Boylan G, et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl Psychiatry. 2016;6(11):e939.CrossRefGoogle Scholar
  78. 78.
    Kelly JR, Allen AP, Temko A, Hutch W, Kennedy PJ, Farid N, et al. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun. 2017;61:50–9.CrossRefGoogle Scholar
  79. 79.
    Jiang C, Li G, Huang P, Liu Z, Zhao B. The gut microbiota and Alzheimer’s disease. J Alzheimers Dis. 2017;58(1):1–15.CrossRefGoogle Scholar
  80. 80.
    Leclercq S, de Timary P, Delzenne NM, Stärkel P. The link between inflammation, bugs, the intestine and the brain in alcohol dependence. Transl Psychiatry. 2017;7(2):e1048.CrossRefGoogle Scholar
  81. 81.
    Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994–1002.CrossRefGoogle Scholar
  82. 82.
    De Leon LM, Watson JB, Kelly CR. Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013;11(8):1036–8.CrossRefGoogle Scholar
  83. 83.
    Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis. 2003;36(5):580–5.CrossRefGoogle Scholar
  84. 84.
    Vandenplas Y, Pierard D, De Greef E. Fecal microbiota transplantation: just a fancy trend? J Pediatr Gastroenterol Nutr. 2015;61(1):4–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Alper Evrensel
    • 1
  • Mehmet Emin Ceylan
    • 1
  1. 1.Department of PsychiatryUskudar UniversityIstanbulTurkey

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