• Alper EvrenselEmail author
  • Barış Önen Ünsalver
  • Mehmet Emin Ceylan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1192)


Psychobiotics are live bacteria that directly and indirectly produce positive effects on neuronal functions by colonizing into the intestinal flora. Preliminary studies, although in limited numbers, have found that these bacteria have anxiolytic and antidepressant activities. No research has yet been published on the antipsychotic efficacy of psychobiotics. However, these preliminary studies have opened up new horizons and raised the idea that a new class is emerging in psychopharmacology. About 70 years have passed since the discovery of chlorpromazine, and while the synaptic transmission is understood in almost all details, there seems to be a paradigm shift in psychopharmacology. In recent years, the perspective has shifted from synapse to intestinal microbiota. In this respect, germ-free and conventional animal experiments and few human studies were examined in a comprehensive manner. In this article, after a brief look at the history of contemporary psychopharmacology, the mechanisms of the gut–brain relationship and the evidence of metabolic, systemic, and neuropsychiatric activities of psychobiotics were discussed in detail. In conclusion, psychobiotics seem to have the potential for treatment of neuropsychiatric disorders in the future. However, there are many questions and we do not know the answers yet. We anticipate that the answer to these questions will be given in the near future.


Probiotics Psychobiotics Microbiota Psychopharmacology Gut–brain axis Dysbiosis 



We would like to thank Dr. Barış Önen Ünsalver for preparing the image used in this review.


  1. 1.
    Köknel O. At the fiftieth anniversary the history of modern psychopharmacology and psychopharmacological researches in Turkey and in the world. Bull Clin Psychopharmacol. 2002;12(4):201–10.Google Scholar
  2. 2.
    Macht DL. Contributions to psychopharmacology. Johns Hopkins Hosp Bull. 1920;31:167–73.Google Scholar
  3. 3.
    Ban TA. Fifty years chlorpromazine: a historical perspective. Neuropsychiatr Dis Treat. 2007;3(4):495–500.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Ban TA. Pharmacotherapy of mental illness. A historical analysis. Progress Neuro Psychopharmacol Biol Psychiatry. 2001;25(4):709–727.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Evrensel A, Önen Ünsalver B, Ceylan ME. Gut-brain axis and psychiatric disorders. Curr Psychiatry Rev. 2018;14(3):178–186.CrossRefGoogle Scholar
  6. 6.
    Ewing JA, Grant WJ. The bromide hazard. South Med J. 1965;58:148–52.PubMedCrossRefGoogle Scholar
  7. 7.
    Lehmann HE. Before they called it psychopharmacology. Neuropsychopharmacology. 1993;8(4):291–303.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Charpentier P, Gailliot P, Jacob R, Gaudechon J, Buisson P. Recherches sur les diméthylaminopropyl-N phénothiazines substituées. Comptes rendus de l’Académie des sciences (Paris). 1952;235:59–60.Google Scholar
  9. 9.
    Laborit H, Huguenard P, Alluaume R. Un noveau stabilisateur vegetatif (le 4560 RP). La Presse Médicale. 1952;60:206–8.PubMedGoogle Scholar
  10. 10.
    Hamon J, Paraire J, Velluz J. Remarques sur l’action du 4560 RP sur l’agitation maniaque. Annales Médico-psychologiques (Paris). 1952;110:331–5.Google Scholar
  11. 11.
    Bowman RL, Caulfield PA, Udenfriend S. Spectrophotometric assay in the visible and ultraviolet. Science. 1955;122(3157):32–3.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Carlsson A, Lindqvist M. Effect of chlorpromazine and haloperidol on formation of 3-methoxytyramine and normetanephrine on mouse brain. Acta Pharmacologica et Toxicologica (Copenh). 1963;20:140–4.CrossRefGoogle Scholar
  13. 13.
    Bennett MR. Monoaminergic synapses and schizophrenia: 45 years of neuroleptics. J Psychopharmacol. 1998;12(3):289–304.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Psychotropic Medications-Consent Drug List Classes of Medications Frequently Used for Psychiatric Indication. Texas Department of State Health Services.
  15. 15.
    Stahl SM. Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. 4th ed. New York: Cambridge University Press; 2013.Google Scholar
  16. 16.
    Stahl SM. Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate. CNS Spectr. 2018;23(3):187–91.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Spohn SN, Mawe GM. Non-conventional features of peripheral serotonin signalling - the gut and beyond. Nat Rev Gastroenterol Hepatol. 2017;14(7):412–20.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Wu H, Denna TH, Storkersen JN, Gerriets VA. Beyond a neurotransmitter: the role of serotonin in inflammation and immunity. Pharmacol Res. 2018. (in press).Google Scholar
  19. 19.
    Gardner A, Boles RG. Is a “mitochondrial psychiatry” in the future? A Rev Curr Psychiatry Rev. 2005;1(3):255–71.CrossRefGoogle Scholar
  20. 20.
    Gardner A, Boles RG. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):730–43.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Han B, Sivaramakrishnan P, Lin CJ, Neve IAA, He J, Tay LWR, et al. Microbial genetic composition tunes host longevity. Cell. 2017;169(7):1249–62.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Anderson G. Linking the biological underpinnings of depression: Role of mitochondria interactions with melatonin, inflammation, sirtuins, tryptophan catabolites, DNA repair and oxidative and nitrosative stress, with consequences for classification and cognition. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80(Pt C):255–66.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PWJ. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends Neurosci. 2016;39(11):763–81.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiat. 2013;74(10):720–6.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Evrensel A, Ceylan ME. Microbiome: the missing link in neuropsychiatric disorders. EMJ Innov. 2017;1(1):83–8.Google Scholar
  26. 26.
    Evrensel A, Ceylan ME. The gut-brain axis: the missing link in depression. Clin Psychopharmacol Neurosci. 2015;13(3):239–44.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Evrensel A, Ceylan ME. Fecal microbiota transplantation and its usage in neuropsychiatric disorders. Clin Psychopharmacol Neurosci. 2016;14(3):231–7.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Rea K, Dinan TG, Cryan JF. The microbiome: a key regulator of stress and neuroinflammation. Neurobiol Stress. 2016;4:23–33.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–41.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Chu H, Mazmanian SK. Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat Immunol. 2013;14(7):668–75.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541–51.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhou W, Lv H, Li MX, Su H, Huang LG, Li J, et al. Protective effects of bifidobacteria on intestines in newborn rats with necrotizing enterocolitis and its regulation on TLR2 and TLR4. Genetics Mol Res. 2015;14(3):11505–14.CrossRefGoogle Scholar
  33. 33.
    Miller AH, Haroon E, Raison CL, Felger JC. Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress Anxiety. 2013;30(4):297–306.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience. 2013;246:199–229.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology. 2010;139(6):2102–12.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Foster JA, McVey Neufeld KA. Gut–brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36(5):305–12.PubMedCrossRefGoogle Scholar
  37. 37.
    Bercik P, Park AJ, Sinclair D, Khoshdel A, Lu J, Huang X, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut–brain communication. Neurogastroenterol Motil. 2011;23(12):1132–9.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Ma X, Mao YK, Wang B, Huizinga JD, Bienenstock J, Kunze W. Lactobacillus reuteri ingestion prevents hyperexcitability of colonic DRG neurons induced by noxious stimuli. Am J Physiol Gastrointest Liver Physiol. 2009; 296(4): G868–G875.PubMedCrossRefGoogle Scholar
  39. 39.
    McVey Neufeld KA, Mao YK, Bienenstock J, Foster JA, Kunze WA. The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol Motil. 2013;25(2):183–8.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Collins J, Borojevic R, Verdu EF, Huizinga JD, Ratcliffe EM. Intestinal microbiota influence the early postnatal development of the enteric nervous system. J Neurogastroenterol Motil. 2014;26(1): 98–107.CrossRefGoogle Scholar
  41. 41.
    Lomasney KW, Houston A, Shanahan F, Dinan TG, Cryan JF, Hyland NP. Selective influence of host micro-biota on cAMP-mediated ion transport in mouse colon. J Neurogastroenterol Motil. 2014;26(6):887–8.CrossRefGoogle Scholar
  42. 42.
    Kabouridis PS, Lasrado R, McCallum S, Chng SH, Snippert HJ, Clevers H, et al. Microbiota controls the homeosta-sis of glial cells in the gut lamina propria. Neuron. 2015;85(2):289–95.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays. 2011;33(8):574–81.CrossRefGoogle Scholar
  44. 44.
    Bonaz B, Sinniger V, Pellissier S. The vagus nerve in the neuro-immune axis: Implications in the pathology of the gastrointestinal tract. Front Immunol. 2017;8:1452.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Mezzacappa ES, Kelsey RM, Katkin ES, Sloan RP. Vagal rebound and recovery from psychological stress. Psychosom Med. 2001;63:650–7.PubMedCrossRefGoogle Scholar
  46. 46.
    de Haan JJ, Hadfoune M, Lubbers T, Hodin C, Lenaerts K, Ito A, et al. Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex. Am J Physiol Gastrointest Liver Physiol. 2013;305(5): G383–G391.Google Scholar
  47. 47.
    Weberruss H, Maucher J, Oberhoffer R, Müller J. Recovery of the cardiac autonomic nervous and vascular system after maximal cardiopulmonary exercise testing in recreational athletes. Eur J Appl Physiol. 2018;118(1):205–11.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Kirchner A, Birklein F, Stefan H, Handwerker HO. Left vagus nerve stimulation suppresses experimentally induced pain. Neurology. 2000;55(8):1167–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Galbarriatu L, Pomposo I, Aurrecoechea J, Marinas A, Agúndez M, Gómez JC, et al. Vagus nerve stimulation therapy for treatment-resistant epilepsy: a 15-year experience at a single institution. Clin Neurol Neurosurg. 2015;137:89–93.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Shah AP, Carreno FR, Wu H, Chung YA, Frazer A. Role of TrkB in the anxiolytic-like and antidepressant-like effects of vagal nerve stimulation: comparison with desipramine. Neuroscience. 2016;322:273–86.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Abdel Salam OM. Fluoxetine and sertraline stimulate gastric acid secretion via a vagal pathway in anaesthetised rats. Pharmacol Res. 2004;50(3):309–16.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Malick M, Gilbert K, Daniel J, Arseneault-Breard J, Tompkins TA, Godbout R, et al. Vagotomy prevents the effect of probiotics on caspase activity in a model of postmyocardial infarction depression. J Neurogastroenterol Motil. 2015;27(5):663–71.CrossRefGoogle Scholar
  53. 53.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Evrensel A, Ceylan ME. Gut-microbiota-brain axis and depression. In: Kim YK, editor. Understanding depression. Singapore: Springer; 2018. p. 197–207.CrossRefGoogle Scholar
  55. 55.
    Zareie M, Johnson-Henry K, Jury J, Yang PC, Ngan BY, McKay DM, et al. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut. 2006;55(11):1553–60.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Ait-Belgnaoui A, Durand H, Cartier C, Chaumaz G, Eutamene H, Ferrier L, et al. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012;37(11):1885–95.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Reandon S. Gut-brain link grabs neuroscientists. Nature. 2014;515(7526):175–7.CrossRefGoogle Scholar
  58. 58.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PW, et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology. 2015;232(10):1793–801.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91–119.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Lei E, Vacy K, Boon WC. Fatty acids and their therapeutic potential in neurological disorders. Neurochem Int. 2016;95:75–84.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Sun J, Wang F, Hong G, Pang M, Xu H, Li H, et al. Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress. Neurosci Lett. 2016;618:159–66.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour–epigenetic regulation of the gut–brain axis. Genes Brain Behav. 2014;13(1):69–86.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965–77.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Morris G, Berk M, Carvalho A, Caso JR, Sanz Y, Walder K, et al. The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmune disease. Mol Neurobiol. 2017;54(6):4432–51.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Indigenous bacteria from the gut micro-biota regulate host serotonin biosynthesis. Cell. 2015;161(2):264–76.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci. 2009;106(10):3698–703.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Mackowiak PA. Recycling Metchnikoff: probiotics, the intestinal microbiome and the quest for long life. Front Public Health. 2013;1:52.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    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
  71. 71.
    Philips JGP. The treatment of melancholia by the lactic acid bacillus. J Ment Sci. 1910;56(234):422–31.CrossRefGoogle Scholar
  72. 72.
    Bambury A, Sandhu K, Cryan JF, Dinan TG. Finding the needle in the haystack: systematic identification of psychobiotics. Br J Pharmacol. 2017. (in press).Google Scholar
  73. 73.
    Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43(2):164–74.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    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.PubMedCrossRefGoogle Scholar
  75. 75.
    Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci. 2011;108(38):16050–5.CrossRefGoogle Scholar
  76. 76.
    Janik R, Thomason LAM, Stanisz AM, Forsythe P, Bienenstock J, Stanisz GJ. Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. NeuroImage. 2016;125:988–95.PubMedCrossRefGoogle Scholar
  77. 77.
    Matthews DM, Jenks SM. Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice. Behav Process. 2013;96:27–35.CrossRefGoogle Scholar
  78. 78.
    Alander M, Satokari R, Korpela R, Saxelin M, Vilpponen-Salmela T, Mattila-Sandholm T, et al. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl Environ Microbiol. 1999;65(1):351–4.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Frese SA, Hutton AA, Contreras LN, Shaw CA, Palumbo MC, Casaburi G, et al. Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants. mSphere. 2017;2(6): pii: e00501–17.Google Scholar
  80. 80.
    Liang S, Wang T, Hu X, Luo J, Li W, Wu X, et al. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress. Neuroscience. 2015;310:561–77.CrossRefGoogle Scholar
  81. 81.
    Moya-Perez A, Perez-Villalba A, Benitez-Paez A, Campillo I, Sanz Y. Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice. Brain Behav Immun. 2017;65:43–56.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    McVey Neufeld KA, Kay S, Bienenstock J. Mouse strain affects behavioral and neuroendocrine stress responses following administration of probiotic Lactobacillus rhamnosus JB-1 or traditional antidepressant fluoxetine. Front Neurosci. 2018;12:294.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007;61(3):355–61.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifi-dobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011;2(4):256–61.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015;48:258–64.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Kato-Kataoka A, Nishida K, Takada M, Kawai M, Kikuchi-Hayakawa H, Suda K, et al. Fermented milk containing Lacto-bacillus casei strain Shirota preserves the diversity of the gut microbiota and relieves abdominal dysfunction in healthy medical students exposed to academic stress. Appl Environ Microbiol. 2016;82(12):3649–58.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Sashihara T, Nagata M, Mori T, Ikegami S, Gotoh M, Okubo K, et al. Effects of Lactobacillus gasseri OLL2809 and α-lactalbumin on university-student athletes: a randomized, double-blind, placebo-controlled clinical trial. Appl Physiol Nutr Metab. 2013;38(12):1228–35.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013;144(7):1394–401.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: A pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153(2):448–459.e8.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Claesson MJ, Cusack S, O’Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, et al. Composition, variability, and tempo-ral stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci. 2011;108(Suppl 1):4586–91.CrossRefGoogle Scholar
  92. 92.
    Abisado RG, Benomar S, Klaus JR, Dandekar AA, Chandler JR. Bacterial quorum sensing and microbial community interactions. MBio. 2018;9(3): pii: e02331–17.Google Scholar
  93. 93.
    Macedo D, Filho AJMC, Soares de Sousa CN, Quevedo J, Barichello T, Junior 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.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Ishijima SA, Abe S. A novel murine candidiasis model with severe colonization in the stomach induced by n-acetylglucosamine-treatment and its scoring system based on local characteristic stomach symptoms. Med Mycol J. 2015;56(4):E31–9.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    López-Muñoz F, Alamo C. Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des. 2009;15(14):1563–86.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Patra S. Psychobiotics: A paradigm shift in psychopharmacology. Indian J Pharmacol. 2016;48(4):469–70.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Sato-Kasai M, Kato TA, Ohgidani M, Mizoguchi Y, Sagata N, Inamine S, et al. Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7. Schizophr Res. 2016;178(1–3):35–43.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Alper Evrensel
    • 1
    Email author
  • Barış Önen Ünsalver
    • 2
  • Mehmet Emin Ceylan
    • 3
  1. 1.Department of PsychiatryUskudar University, NP Brain HospitalUmraniye, IstanbulTurkey
  2. 2.Department of Medical Documentation and Secretariat, Vocational School of Health ServicesUskudar UniversityIstanbulTurkey
  3. 3.Departments of Psychology and PhilosophyUskudar UniversityIstanbulTurkey

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