Journal of Microbiology

, Volume 56, Issue 3, pp 172–182 | Cite as

Mind-altering with the gut: Modulation of the gut-brain axis with probiotics

  • Namhee Kim
  • Misun Yun
  • Young Joon Oh
  • Hak-Jong ChoiEmail author
Review Human Microbiomes and Probiotics


It is increasingly evident that bidirectional interactions exist among the gastrointestinal tract, the enteric nervous system, and the central nervous system. Recent preclinical and clinical trials have shown that gut microbiota plays an important role in these gut-brain interactions. Furthermore, alterations in gut microbiota composition may be associated with pathogenesis of various neurological disorders, including stress, autism, depression, Parkinson’s disease, and Alzheimer’s disease. Therefore, the concepts of the microbiota-gut-brain axis is emerging. Here, we review the role of gut microbiota in bidirectional interactions between the gut and the brain, including neural, immune-mediated, and metabolic mechanisms. We highlight recent advances in the understanding of probiotic modulation of neurological and neuropsychiatric disorders via the gut-brain axis.


probiotics gut microbiota nervous system gutbrain axis gut dysbiosis neurological disorders 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, J.B., Johansen, L.J., Powell, L.D., Quig, D., and Rubin, R.A. 2011. Gastrointestinal flora and gastrointestinal status in children with autism-comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 11, 22.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Aizawa, E., Tsuji, H., Asahara, T., Takahashi, T., Teraishi, T., Yoshida, S., Ota, M., Koga, N., Hattori, K., and Kunugi, H. 2016. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J. Affect. Disord. 202, 254–257.PubMedCrossRefGoogle Scholar
  3. Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O.R., Hamidi, G.A., and Salami, M. 2016. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer’s disease: A randomized, double-blind and controlled trial. Front. Aging Neurosci. 8, 256.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bailey, M.T. and Coe, C.L. 1999. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev. Psychobiol. 35, 146–155.PubMedCrossRefGoogle Scholar
  5. Bailey, M.T., Dowd, S.E., Galley, J.D., Hufnagle, A.R., Allen, R.G., and Lyte, M. 2011. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav. Immun. 25, 397–407.PubMedCrossRefGoogle Scholar
  6. Bailey, M.T., Dowd, S.E., Parry, N.M., Galley, J.D., Schauer, D.B., and Lyte, M. 2010. Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by Citrobacter rodentium. Infect. Immun. 78, 1509–1519.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bailey, M.T., Lubach, G.R., and Coe, C.L. 2004. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J. Pediatr. Gastroenterol. Nutr. 38, 414–421.PubMedCrossRefGoogle Scholar
  8. Banks, W.A. 2005. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr. Pharm. Des. 11, 973–984.PubMedCrossRefGoogle Scholar
  9. Barrett, E., Ross, R.P., O’Toole, P.W., Fitzgerald, G.F., and Stanton, C. 2012. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 113, 411–417.PubMedCrossRefGoogle Scholar
  10. Bengmark, S. 2013. Gut microbiota, immune development and function. Pharmacol. Res. 69, 87–113.PubMedCrossRefGoogle Scholar
  11. Benton, D., Williams, C., and Brown, A. 2007. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61, 355–361.PubMedCrossRefGoogle Scholar
  12. Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K.D., et al. 2011a. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141, 599–609.PubMedCrossRefGoogle Scholar
  13. Bercik, P., Park, A.J., Sinclair, D., Khoshdel, A., Lu, J., Huang, X., Deng, Y., Blennerhassett, P.A., Fahnestock, M., Moine, D., et al. 2011b. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol. Motil. 23, 1132–1139.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Berer, K. and Krishnamoorthy, G. 2012. Commensal gut flora and brain autoimmunity: A love or hate affair? Acta Neuropathol. 123, 639–651.PubMedCrossRefGoogle Scholar
  15. Bermudez-Brito, M., Plaza-Diaz, J., Munoz-Quezada, S., Gomez-Llorente, C., and Gil, A. 2012. Probiotic mechanisms of action. Ann. Nutr. Metab. 61, 160–174.PubMedCrossRefGoogle Scholar
  16. Boursi, B., Mamtani, R., Haynes, K., and Yang, Y.X. 2016. Parkinson’s disease and colorectal cancer risk-A nested case control study. Cancer Epidemiol. 43, 9–14.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bravo, J.A., Forsythe, P., Chew, M.V., Escaravage, E., Savignac, H.M., Dinan, T.G., Bienenstock, J., and Cryan, J.F. 2011. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA 108, 16050–16055.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bravo, J.A., Julio-Pieper, M., Forsythe, P., Kunze, W., Dinan, T.G., Bienenstock, J., and Cryan, J.F. 2012. Communication between gastrointestinal bacteria and the nervous system. Curr. Opin. Pharmacol. 12, 667–672.PubMedCrossRefGoogle Scholar
  19. Browning, K.N., Verheijden, S., and Boeckxstaens, G.E. 2017. The vagus nerve in appetite regulation, mood, and intestinal inflammation. Gastroenterology 152, 730–744.PubMedCrossRefGoogle Scholar
  20. Bu, X.L., Yao, X.Q., Jiao, S.S., Zeng, F., Liu, Y.H., Xiang, Y., Liang, C.R., Wang, Q.H., Wang, X., Cao, H.Y., et al. 2015. A study on the association between infectious burden and Alzheimer’s disease. Eur. J. Neurol. 22, 1519–1525.PubMedCrossRefGoogle Scholar
  21. Carabotti, M., Scirocco, A., Maselli, M.A., and Severi, C. 2015. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann.Gastroenterol. 28, 203–209.PubMedPubMedCentralGoogle Scholar
  22. Cassani, E., Barichella, M., Cancello, R., Cavanna, F., Iorio, L., Cereda, E., Bolliri, C., Zampella Maria, P., Bianchi, F., Cestaro, B., et al. 2015. Increased urinary indoxyl sulfate (indican): New insights into gut dysbiosis in Parkinson’s disease. Parkinsonism. Relat. Disord. 21, 389–393.PubMedCrossRefGoogle Scholar
  23. Cassani, E., Privitera, G., Pezzoli, G., Pusani, C., Madio, C., Iorio, L., and Barichella, M. 2011. Use of probiotics for the treatment of constipation in Parkinson’s disease patients. Minerva Gastroenterol. Dietol. 57, 117–121.PubMedGoogle Scholar
  24. Choi, H.J., Lee, N.K., and Paik, H.D. 2015. Health benefits of lactic acid bacteria isolated from kimchi, with respect to immunomodulatory effects. Food Sci. Biotechnol. 24, 783–789.CrossRefGoogle Scholar
  25. Clarke, M.B., Hughes, D.T., Zhu, C., Boedeker, E.C., and Sperandio, V. 2006. The QseC sensor kinase: a bacterial adrenergic receptor. Proc. Natl. Acad. Sci. USA 103, 10420–10425.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Cohen, L.J., Esterhazy, D., Kim, S.H., Lemetre, C., Aguilar, R.R., Gordon, E.A., Pickard, A.J., Cross, J.R., Emiliano, A.B., Han, S.M., et al. 2017. Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature 549, 48–53.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Coury, D.L., Ashwood, P., Fasano, A., Fuchs, G., Geraghty, M., Kaul, A., Mawe, G., Patterson, P., and Jones, N.E. 2012. Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics 130 Suppl 2, S160–S168.PubMedCrossRefGoogle Scholar
  28. Cryan, J.F. and Dinan, T.G. 2012. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13, 701–712.PubMedCrossRefGoogle Scholar
  29. De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. 2013. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 8, e76993.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Desbonnet, L., Garrett, L., Clarke, G., Bienenstock, J., and Dinan, T.G. 2008. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J. Psychiatr. Res. 43, 164–174.PubMedCrossRefGoogle Scholar
  31. Desbonnet, L., Garrett, L., Clarke, G., Kiely, B., Cryan, J.F., and Dinan, T.G. 2010. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170, 1179–1188.PubMedCrossRefGoogle Scholar
  32. Deshmukh, H.S., Liu, Y., Menkiti, O.R., Mei, J., Dai, N., O’Leary, C.E., Oliver, P.M., Kolls, J.K., Weiser, J.N., and Worthen, G.S. 2014. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat. Med. 20, 524–530.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Diamond, B., Huerta, P.T., Tracey, K., and Volpe, B.T. 2011. It takes guts to grow a brain: Increasing evidence of the important role of the intestinal microflora in neuro-and immune-modulatory functions during development and adulthood. Bioessays 33, 588–591.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Donato, K.A., Gareau, M.G., Wang, Y.J., and Sherman, P.M. 2010. Lactobacillus rhamnosus GG attenuates interferon-γ and tumour necrosis factor-a-induced barrier dysfunction and pro-inflammatory signalling. Microbiology 156, 3288–3297.PubMedCrossRefGoogle Scholar
  35. Emery, D.C., Shoemark, D.K., Batstone, T.E., Waterfall, C.M., Coghill, J.A., Cerajewska, T.L., Davies, M., West, N.X., and Allen, S.J. 2017. 16S rRNA next generation sequencing analysis shows bacteria in Alzheimer’s post-mortem brain. Front. Aging Neurosci. 9, 195.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Erny, D., de Angelis, A.L.H., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., and Buch, T. 2015. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18, 965–977.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Felger, J.C. and Lotrich, F.E. 2013. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 246, 199–229.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Finegold, S.M., Dowd, S.E., Gontcharova, V., Liu, C., Henley, K.E., Wolcott, R.D., Youn, E., Summanen, P.H., Granpeesheh, D., Dixon, D., et al. 2010. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16, 444–453.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Forsyth, C.B., Shannon, K.M., Kordower, J.H., Voigt, R.M., Shaikh, M., Jaglin, J.A., Estes, J.D., Dodiya, H.B., and Keshavarzian, A. 2011. Increased intestinal permeability correlates with sigmoid mucosa a-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS One 6, e28032.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Frost, G., Sleeth, M.L., Sahuri-Arisoylu, M., Lizarbe, B., Cerdan, S., Brody, L., Anastasovska, J., Ghourab, S., Hankir, M., Zhang, S., et al. 2014. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 5, 3611.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450.PubMedCrossRefGoogle Scholar
  42. Gagliano, H., Delgado-Morales, R., Sanz-Garcia, A., and Armario, A. 2014. High doses of the histone deacetylase inhibitor sodium butyrate trigger a stress-like response. Neuropharmacology 79, 75–82.PubMedCrossRefGoogle Scholar
  43. Gill, S.R., Pop, M., Deboy, R.T., Eckburg, P.B., Turnbaugh, P.J., Samuel, B.S., Gordon, J.I., Relman, D.A., Fraser-Liggett, C.M., and Nelson, K.E. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Goehler, L.E., Park, S.M., Opitz, N., Lyte, M., and Gaykema, R.P. 2008. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav. Immun. 22, 354–366.PubMedCrossRefGoogle Scholar
  45. Goldstone, A.P. 2006. The hypothalamus, hormones, and hunger: alterations in human obesity and illness. Prog. Brain Res. 153, 57–73.PubMedCrossRefGoogle Scholar
  46. Golubeva, A.V., Crampton, S., Desbonnet, L., Edge, D., O’Sullivan, O., Lomasney, K.W., Zhdanov, A.V., Crispie, F., Moloney, R.D., Borre, Y.E., et al. 2015. Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood. Psychoneuroendocrinology 60, 58–74.PubMedCrossRefGoogle Scholar
  47. Grenham, S., Clarke, G., Cryan, J.F., and Dinan, T.G. 2011. Brain-gutmicrobe communication in health and disease. Front. Physiol. 2, 94.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Grossi, E., Melli, S., Dunca, D., and Terruzzi, V. 2016. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Med. Case Rep. 4, 2050313x16666231.Google Scholar
  49. Guthrie, G.D. and Nicholson-Guthrie, C.S. 1989. γ-Aminobutyric acid uptake by a bacterial system with neurotransmitter binding characteristics. Proc. Natl. Acad. Sci. USA 86, 7378–7381.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Harach, T., Marungruang, N., Duthilleul, N., Cheatham, V., Mc Coy, K.D., Frisoni, G., Neher, J.J., Fak, F., Jucker, M., Lasser, T., et al. 2017. Reduction of Aβ amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci. Rep. 7, 41802.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Hardy, J. and Selkoe, D.J. 2002. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356.PubMedCrossRefGoogle Scholar
  52. Hemarajata, P., Gao, C., Pflughoeft, K.J., Thomas, C.M., Saulnier, D.M., Spinler, J.K., and Versalovic, J. 2013. Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri. J. Bacteriol. 195, 5567–5576.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Hill, C., Guarner, F., Reid, G., Gibson, G.R., Merenstein, D.J., Pot, B., Morelli, L., Canani, R.B., Flint, H.J., Salminen, S., et al. 2014. Expert consensus document. The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11, 506–514.PubMedGoogle Scholar
  54. Holzer, P. and Farzi, A. 2014. Neuropeptides and the microbiotagut-brain axis. Adv. Exp. Med. Biol. 817, 195–219.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Horn, T. and Klein, J. 2013. Neuroprotective effects of lactate in brain ischemia: dependence on anesthetic drugs. Neurochem. Int. 62, 251–257.PubMedCrossRefGoogle Scholar
  56. Hosoi, T., Okuma, Y., and Nomura, Y. 2002. The mechanisms of immune-to-brain communication in inflammation as a drug target. Curr. Drug Targets Inflamm. Allergy 1, 257–262.PubMedCrossRefGoogle Scholar
  57. Hsiao, E.Y., McBride, S.W., Hsien, S., Sharon, G., Hyde, E.R., McCue, T., Codelli, J.A., Chow, J., Reisman, S.E., Petrosino, J.F., et al. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Inan, M.S., Rasoulpour, R.J., Yin, L., Hubbard, A.K., Rosenberg, D.W., and Giardina, C. 2000. The luminal short-chain fatty acid butyrate modulates NF-kB activity in a human colonic epithelial cell line. Gastroenterology 118, 724–734.PubMedCrossRefGoogle Scholar
  59. Janik, R., Thomason, L.A.M., Stanisz, A.M., Forsythe, P., Bienenstock, J., and Stanisz, G.J. 2016. Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. Neuroimage 125, 988–995.PubMedCrossRefGoogle Scholar
  60. Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y., Wang, W., Tang, W., Tan, Z., Shi, J., et al. 2015. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav. Immun. 48, 186–194.PubMedCrossRefGoogle Scholar
  61. Kabouridis, P.S., Lasrado, R., McCallum, S., Chng, S.H., Snippert, H.J., Clevers, H., Pettersson, S., and Pachnis, V. 2015. Microbiota controls the homeostasis of glial cells in the gut lamina propria. Neuron 85, 289–295.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Kaluzna-Czaplinska, J. and Blaszczyk, S. 2012. The level of arabinitol in autistic children after probiotic therapy. Nutrition 28, 124–126.PubMedCrossRefGoogle Scholar
  63. Kang, D.W., Park, J.G., Ilhan, Z.E., Wallstrom, G., Labaer, J., Adams, J.B., and Krajmalnik-Brown, R. 2013. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One 8, e68322.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Kato-Kataoka, A., Nishida, K., Takada, M., Kawai, M., Kikuchi-Hayakawa, H., Suda, K., Ishikawa, H., Gondo, Y., Shimizu, K., Matsuki, T., et al. 2016. Fermented milk containing Lactobacillus 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. 82, 3649–3658.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Kawashima, K., Misawa, H., Moriwaki, Y., Fujii, Y.X., Fujii, T., Horiuchi, Y., Yamada, T., Imanaka, T., and Kamekura, M. 2007. Ubiquitous expression of acetylcholine and its biological functions in life forms without nervous systems. Life Sci. 80, 2206–2209.PubMedCrossRefGoogle Scholar
  66. Keshavarzian, A., Green, S.J., Engen, P.A., Voigt, R.M., Naqib, A., Forsyth, C.B., Mutlu, E., and Shannon, K.M. 2015. Colonic bacterial composition in Parkinson’s disease. Mov. Disord. 30, 1351–1360.PubMedCrossRefGoogle Scholar
  67. Kimura, I., Ozawa, K., Inoue, D., Imamura, T., Kimura, K., Maeda, T., Terasawa, K., Kashihara, D., Hirano, K., Tani, T., et al. 2013. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat. Commun. 4, 1829.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Kunze, W.A., Mao, Y.K., Wang, B., Huizinga, J.D., Ma, X., Forsythe, P., and Bienenstock, J. 2009. Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J. Cell Mol. Med. 13, 2261–2270.PubMedCrossRefGoogle Scholar
  69. Landete, J.M., De las Rivas, B., Marcobal, A., and Munoz, R. 2008. Updated molecular knowledge about histamine biosynthesis by bacteria. Crit. Rev. Food Sci. Nutr. 48, 697–714.PubMedCrossRefGoogle Scholar
  70. Lim, S.K., Kwon, M.S., Lee, J., Oh, Y.J., Jang, J.Y., Lee, J.H., Park, H.W., Nam, Y.D., Seo, M.J., Roh, S.W., et al. 2017. Weissella cibaria WIKIM28 ameliorates atopic dermatitis-like skin lesions by inducing tolerogenic dendritic cells and regulatory T cells in BALB/c mice. Sci. Rep. 7, 40040.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Liu, X., Cao, S., and Zhang, X. 2015. Modulation of gut microbiotabrain axis by probiotics, prebiotics, and diet. J. Agric. Food Chem. 63, 7885–7895.PubMedCrossRefGoogle Scholar
  72. Louveau, A., Smirnov, I., Keyes, T.J., Eccles, J.D., Rouhani, S.J., Peske, J.D., Derecki, N.C., Castle, D., Mandell, J.W., Lee, K.S., et al. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337–341.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Lyte, M. 2011. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. BioEssays 33, 574–581.PubMedCrossRefGoogle Scholar
  74. Macfabe, D.F. 2012. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microb. Ecol. Health Dis. 23, 19260.Google Scholar
  75. Macfarlane, S. and Macfarlane, G.T. 2003. Regulation of short-chain fatty acid production. Proc. Nutr. Soc. 62, 67–72.PubMedCrossRefGoogle Scholar
  76. Macpherson, A.J. and Uhr, T. 2004. Compartmentalization of the mucosal immune responses to commensal intestinal bacteria. Ann. N. Y. Acad. Sci. 1029, 36–43.PubMedCrossRefGoogle Scholar
  77. McCusker, R.H. and Kelley, K.W. 2013. Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J. Exp. Biol. 216, 84–98.PubMedPubMedCentralCrossRefGoogle Scholar
  78. McVey Neufeld, K.A., Mao, Y.K., Bienenstock, J., Foster, J.A., and Kunze, W.A. 2013. The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol. Motil. 25, e183–e188.CrossRefGoogle Scholar
  79. Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., Bisson, J.F., Rougeot, C., Pichelin, M., Cazaubiel, M., et al. 2011a. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr. 105, 755–764.PubMedCrossRefGoogle Scholar
  80. Messaoudi, M., Violle, N., Bisson, J.F., Desor, D., Javelot, H., and Rougeot, C. 2011b. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut microbes 2, 256–261.PubMedCrossRefGoogle Scholar
  81. Meuer, K., Pitzer, C., Teismann, P., Kruger, C., Goricke, B., Laage, R., Lingor, P., Peters, K., Schlachetzki, J.C., Kobayashi, K., et al. 2006. Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson’s disease. J. Neurochem. 97, 675–686.PubMedCrossRefGoogle Scholar
  82. Miller, A.H., Haroon, E., Raison, C.L., and Felger, J.C. 2013. Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress. Anxiety 30, 297–306.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Mountzouris, K.C., Tsirtsikos, P., Kalamara, E., Nitsch, S., Schatzmayr, G., and Fegeros, K. 2007. Evaluation of the efficacy of a probiotic containing Lactobacillus, Bifidobacterium, Enterococcus, and Pediococcus strains in promoting broiler performance and modulating cecal microflora composition and metabolic activities. Poult. Sci. 86, 309–317.PubMedCrossRefGoogle Scholar
  84. O’Mahony, L., McCarthy, J., Kelly, P., Hurley, G., Luo, F., Chen, K., O’Sullivan, G.C., Kiely, B., Collins, J.K., Shanahan, F., et al. 2005. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128, 541–551.PubMedCrossRefGoogle Scholar
  85. O’Mahony, S.M., Marchesi, J.R., Scully, P., Codling, C., Ceolho, A.M., Quigley, E.M., Cryan, J.F., and Dinan, T.G. 2009. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol. Psychiatry 65, 263–267.PubMedCrossRefGoogle Scholar
  86. Obermeier, B., Daneman, R., and Ransohoff, R.M. 2013. Development, maintenance and disruption of the blood-brain barrier. Nat. Med. 19, 1584–1596.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Overduin, J., Schoterman, M.H., Calame, W., Schonewille, A.J., and Ten Bruggencate, S.J. 2013. Dietary galacto-oligosaccharides and calcium: effects on energy intake, fat-pad weight and satiety-related, gastrointestinal hormones in rats. Br. J. Nutr. 109, 1338–1348.PubMedCrossRefGoogle Scholar
  88. Özogul, F. 2011. Effects of specific lactic acid bacteria species on biogenic amine production by foodborne pathogen. Int. J. Food Sci. Technol. 46, 478–484.CrossRefGoogle Scholar
  89. Parracho, H.M., Bingham, M.O., Gibson, G.R., and McCartney, A.L. 2005. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J. Med. Microbiol. 54, 987–991.PubMedCrossRefGoogle Scholar
  90. Prakash, A., Medhi, B., and Chopra, K. 2013. Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-beta induced experimental model of Alzheimer’s disease. Pharmacol. Biochem. Behav. 110, 46–57.PubMedCrossRefGoogle Scholar
  91. Psichas, A., Sleeth, M.L., Murphy, K.G., Brooks, L., Bewick, G.A., Hanyaloglu, A.C., Ghatei, M.A., Bloom, S.R., and Frost, G. 2015. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int. J. Obes. (Lond) 39, 424–429.CrossRefGoogle Scholar
  92. Rafiki, A., Boulland, J.L., Halestrap, A.P., Ottersen, O.P., and Bergersen, L. 2003. Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 122, 677–688.PubMedCrossRefGoogle Scholar
  93. Rhee, S.H., Pothoulakis, C., and Mayer, E.A. 2009. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol. 6, 306–314.PubMedCrossRefGoogle Scholar
  94. Rios-Covian, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., de Los Reyes-Gavilan, C.G., and Salazar, N. 2016. Intestinal short chain fatty acids and their link with diet and human health. Front. Microbiol. 7, 185.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Sarkar, A., Lehto, S.M., Harty, S., Dinan, T.G., Cryan, J.F., and Burnet, P.W. 2016. Psychobiotics and the manipulation of bacteria-gutbrain signals. Trends Neurosci. 39, 763–781.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Savignac, H.M., Kiely, B., Dinan, T.G., and Cryan, J.F. 2014. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol. Motil. 26, 1615–1627.PubMedCrossRefGoogle Scholar
  97. Scheperjans, F., Aho, V., Pereira, P.A., Koskinen, K., Paulin, L., Pekkonen, E., Haapaniemi, E., Kaakkola, S., Eerola-Rautio, J., Pohja, M., et al. 2015. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov. Disord. 30, 350–358.PubMedCrossRefGoogle Scholar
  98. Shyu, W.C., Lin, S.Z., Yang, H.I., Tzeng, Y.S., Pang, C.Y., Yen, P.S., and Li, H. 2004. Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110, 1847–1854.PubMedCrossRefGoogle Scholar
  99. Song, Y., Liu, C., and Finegold, S.M. 2004. Real-time PCR quantitation of clostridia in feces of autistic children. Appl. Environ. Microbiol. 70, 6459–6465.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J.A., and Colzato, L.S. 2015. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav. Immun. 48, 258–264.PubMedCrossRefGoogle Scholar
  101. Stilling, R.M., Dinan, T.G., and Cryan, J.F. 2014. Microbial genes, brain & behaviour -epigenetic regulation of the gut-brain axis. Genes Brain Behav. 13, 69–86.PubMedCrossRefGoogle Scholar
  102. Strati, F., Cavalieri, D., Albanese, D., De Felice, C., Donati, C., Hayek, J., Jousson, O., Leoncini, S., Renzi, D., Calabro, A., et al. 2017. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 5, 24.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X.N., Kubo, C., and Koga, Y. 2004. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 558, 263–275.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Sun, B.L., Wang, L.H., Yang, T., Sun, J.Y., Mao, L.L., Yang, M.F., Yuan, H., Colvin, R.A., and Yang, X.Y. 2017. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases. Prog. Neurobiol. doi: 10.1016/j.pneurobio.2017.08.007 (in press).Google Scholar
  105. Surwase, S.N. and Jadhav, J.P. 2011. Bioconversion of L-tyrosine to L-DOPA by a novel bacterium Bacillus sp. JPJ. Amino Acids 41, 495–506.PubMedCrossRefGoogle Scholar
  106. Thayer, J.F. and Sternberg, E.M. 2009. Neural concomitants of immunity-focus on the vagus nerve. Neuroimage 47, 908–910.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Thomas, C.M., Hong, T., van Pijkeren, J.P., Hemarajata, P., Trinh, D.V., Hu, W., Britton, R.A., Kalkum, M., and Versalovic, J. 2012. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One 7, e31951.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Tillisch, K. 2014. The effects of gut microbiota on CNS function in humans. Gut Microbes 5, 404–410.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain-Raspaud, S., Trotin, B., Naliboff, B., et al. 2013. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144, 1394–1401.e4.PubMedCrossRefGoogle Scholar
  110. Tremaroli, V. and Backhed, F. 2012. Functional interactions between the gut microbiota and host metabolism. Nature 489, 242–249.PubMedCrossRefGoogle Scholar
  111. Vetulani, J. 2013. Early maternal separation: a rodent model of depression and a prevailing human condition. Pharmacol. Rep. 65, 1451–1461.PubMedCrossRefGoogle Scholar
  112. Vogt, N.M., Kerby, R.L., Dill-McFarland, K.A., Harding, S.J., Merluzzi, A.P., Johnson, S.C., Carlsson, C.M., Asthana, S., Zetterberg, H., and Blennow, K. 2017. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 7, 13537.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Wallner, S., Peters, S., Pitzer, C., Resch, H., Bogdahn, U., and Schneider, A. 2015. The granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity. Front. Cell Dev. Biol. 3, 48.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Wang, L., Christophersen, C.T., Sorich, M.J., Gerber, J.P., Angley, M.T., and Conlon, M.A. 2011. Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Appl. Environ. Microbiol. 77, 6718–6721.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Wang, L., Christophersen, C.T., Sorich, M.J., Gerber, J.P., Angley, M.T., and Conlon, M.A. 2013. Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol. Autism 4, 42.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Wang, Y. and Kasper, L.H. 2014. The role of microbiome in central nervous system disorders. Brain. Behav. Immun. 38, 1–12.PubMedCrossRefGoogle Scholar
  117. Westfall, S., Lomis, N., Kahouli, I., Dia, S.Y., Singh, S.P., and Prakash, S. 2017. Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis. Cell. Mol. Life Sci. 74, 3769–3787.PubMedCrossRefGoogle Scholar
  118. Williams, B.B., Van Benschoten, A.H., Cimermancic, P., Donia, M.S., Zimmermann, M., Taketani, M., Ishihara, A., Kashyap, P.C., Fraser, J.S., and Fischbach, M.A. 2014. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe 16, 495–503.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Yang, N.J. and Chiu, I.M. 2017. Bacterial signaling to the nervous system through toxins and metabolites. J. Mol. Biol. 429, 587–605.PubMedPubMedCentralCrossRefGoogle Scholar
  120. Yano, J.M., Yu, K., Donaldson, G.P., Shastri, G.G., Ann, P., Ma, L., Nagler, C.R., Ismagilov, R.F., Mazmanian, S.K., and Hsiao, E.Y. 2015. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264–276.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Namhee Kim
    • 1
  • Misun Yun
    • 1
  • Young Joon Oh
    • 1
  • Hak-Jong Choi
    • 1
    Email author
  1. 1.Microbiology and Functionality Research GroupWorld Institute of KimchiGwangjuRepublic of Korea

Personalised recommendations