Main Article Content


S.A. Starovoitova

National University of Food Technologies, 68, Volodymyrska str, Kyiv, 01601, Ukraine


The functional connection between the gastrointestinal tract and the central nervous system of the host organism was considered. The relationship between the intestinal microbiome and the central nervous system had been analyzed. The main mechanisms of the influence of microbiota on the functions of the central nervous system were shown. The literature data on the role of the intestinal microbiome in disorders of the central nervous system were summarized. The main factors linking the intestinal microbiota and the central nervous system were given. The prospects of using bacteriotherapeutic drugs and functional food products enriched with appropriate probiotic microorganisms for the prevention and treatment of neurological disorders, as well as for maintaining the functionality of the immune system in stress subjects were highlighted.


gut microbiota, probiotics, stress, central nervous system

Article Details


Ritvanen T., Louhevaara V., Helin P., Väisänen S., Hänninen O. Responses of the autonomic nervous system during periods of perceived high and low work stress in younger and older female teachers. Applied Ergonomics, 2006, vol. 37, no. 3, pp. 311-318. doi: 10.1016/j.apergo.2005.06.013.

Starovoitova S.A., Karpov A.V. Immunobiotics and their effects on the human immune system in health and disease. Biotechnology. Theory and Practice, 2015, no. 4, pp. 10-20. doi: 10.11134/btp.4.2015.2.

Weiss G.A., Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cellular and Molecular Life Sciences, 2017, vol. 74, no. 16, pp. 2959-2677. doi: 10.1007/s00018-017-2509-x.

Belkaid Y., Naik S. Compartmentalized and systemic control of tissue immunity by commensals. Nature immunology, 2013, vol. 14, no. 7, pp. 646-653. doi: 10.1038/ni.2604.

Castellazzi A., Tagliacarne S.C., Soldi S., Valsecchi C. Stress and immune function: there is a role for the gut microbiota? 9th Probiotics, prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition and Human and Microbiota Health. Università Urbaniana. Rome, September 10-12, 2017, pp. 19.

He C.S., Tsai M.L., Ko M.H., Chang C.K., Fang S.H. Relationships among salivary immunoglobulin A, lactoferrin and cortisol in basketball players during a basketball season. European Journal of Applied Physiology, 2010, vol. 110, no. 5, pp. 989-995. doi: 10.1007/s00421-010-1574-8.

Corthesy B. Multi-faceted functions of secretory IgA at mucosal surfaces. Frontiers in immunology, 2013, vol. 4, 185, pp. 1-11. doi: 10.3389/fimmu.2013.00185.

Aidy E.S., Dinan T.G., Cryan J.F. Immune modulation of the brain-gut-microbiome axis. Frontiers in immunology, 2014, vol. 5, 146, pp. 1-4. doi: 10.3389/fmicb.2014.00146.

Sekirov I., Russell S.L., Antunes L.C., Finlay B.B. Gut microbiota in health and disease. Physiological reviews, 2010, vol. 90, no. 3, pp. 859-904. doi: 10.1152/physrev.00045.2009.

Abt M.C., Osborne L.C., Monticelli L.A. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity, 2012, vol. 37, no. 1, pp. 158-170. doi: 10.1016/j.immuni.2012.04.011.

Ichinohe T., Pang I.K., Kumamoto Y. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proceedings of the National Academy of Sciences of the United States of America, 2011, vol. 108, no. 13, pp. 5354-5359. doi: 10.1073/pnas.1019378108.

Berer K., Krishnamoorthy G. Commensal gut flora and brain autoimmunity: a love or hate affair? Acta neuropathological, 2012, vol. 123, no. 5, pp. 639-651. doi: 10.1007/s00401-012-0949-9.

Galland L. The gut microbiome and the braine. Journal of Medical Food, 2014, vol. 17, no. 12, pp. 1261-1272. doi: 10.1089/jmf.2014.7000.

Starovoitova S. Probiotics and stress. Vestnik of the South-Kazakhstan state pharmaceutical academy, 2017, vol. 3, no. 4, pp. 6-7.

Brown E.M., Sadarangani M., Finlay B.B. The role of the immune system in governing host-microbe interactions in the intestine. Nature immunology, 2013, vol. 14, no. 7, pp. 660-667. doi: 10.1038/ni.2611.

Romijn J.A., Corssmit E.P., Havekes L.M., Pijl H. Gut-brain axis. Current opinion in clinical nutrition and metabolic care, 2008, vol. 11, no. 4, pp. 518-521. doi: 10.1097/MCO.0b013e328302c9b0.

Cummings D.E., Overduin J. Gastrointestinal regulation of food intake. The Journal of clinical investigation, 2007, vol. 117, no. 1, pp. 13-23. doi: 10.1172/JCI30227.

Cryan J.F., Dinan T.G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature reviews. Neuroscience, 2012, vol. 13, no. 10, pp. 701-712. doi: 10.1038/nrn3346.

Santos J., Yang P.C., Soderholm J.D., Benjamin M., Perdue M.H. Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut, 2001, vol. 48, no. 5, pp. 630-636. doi: 10.1136/gut.48.5.630.

Al-Asmakh M., Anuar F., Zadjali F., Rafter J., Pettersson S. Gut microbial communities modulating brain development and function. Gut microbes, 2012, vol. 3, no. 4, pp. 366-373. doi: 10.4161/gmic.21287.

Douglas-Escobar M., Elliott E., Neu J. Effect of intestinal microbial ecology on the developing brain. JAMA pediatrics, 2013, vol. 167, no. 4, pp. 374-379. doi: 10.1001/jamapediatrics.2013.497.

O'Malley D., Quigley E.M., Dinan T.G., Cryan J.F. Do interactions between stress and immune responses lead to symptom exacerbations in irritable bowel syndrome? Brain, behavior, and immunity, 2011, vol. 25, no. 7, pp. 1333-1341. doi: 10.1016/j.bbi.2011.04.009.

Bonaz B.L., Bernstein C.N. Brain-gut interactions in inflammatory bowel disease. Gastroenterology, 2013, vol. 144, no. 1, pp. 36-49. doi: 10.1053/j.gastro.2012.10.003.

de Lartigue G., de La Serre C.B., Raybould H.E. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin. Physiology & behavior, 2011, vol. 105, no. 1, pp. 100-105. doi: 10.1016/j.physbeh.2011.02.040.

Mao Y.K., Kasper D.L., Wang B., Forsythe P., Bienenstock J., Kunze W.A. Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nature communications, 2013, vol. 4, pp. 1465. doi: 10.1038/ncomms2478.

Sudo N. Role of microbiome in regulating the HPA axis and its relevance to allergy. Chemical immunology and allergy, 2012, vol. 98, pp. 163-175. doi: 10.1159/000336510.

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. European journal of nutrition, 2013, vol. 53, no. 3, pp. 813-821. doi: 10.1007/s00394-013-0585-8.

Barrett E., Ross R.P., O'Toole P.W., Fitzgerald G.F., Stanton C. Gamma-Aminobutyric acid production by culturable bacteria from the human intestine. Journal of applied microbiology, 2012, vol. 113, no. 2, pp. 411-417. doi: 10.1111/j.1365-2672.2012.05344.x.

Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. BioEssays: news and reviews in molecular, cellular and developmental biology, 2011, vol. 33, no. 8, pp. 574-581. doi: 10.1002/bies.201100024.

Forsythe P., Sudo N., Dinan T., Taylor V.H., Bienenstock J. Mood and gut feelings. Brain, behavior, and immunity, 2010, vol. 24, no. 1, pp. 9-16. doi: 10.1016/j.bbi.2009.05.058.

Rook G.A., Lowry C.A., Raison C.L. Lymphocytes in neuroprotection, cognition and emotion: is intolerance really the answer? Brain, behavior, and immunity, 2011, vol. 25, no. 4, pp. 591-601. doi: 10.1016/j.bbi.2010.12.005.

Ochoa-Reparaz J., Mielcarz D.W., Begum-Haque S., Kasper L.H. Gut, bugs, and brain: role of commensal bacteria in the control of central nervous system disease. Annals of neurology, 2011, vol. 69, no. 2, pp. 240-247. doi: 10.1002/ana.22344.

Brahic M. Multiple sclerosis and viruses. Annals of neurology, 2010, vol. 68, no. 1, pp. 6-8. doi: 10.1002/ana.22057.

Berer K., Mues M., Koutrolos M. et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature, 2011, vol. 479, pp. 538-541. doi: 10.1038/nature10554.

Lee Y.K., Menezes J.S., Umesaki Y., Mazmanian S.K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the United States of America, 2011, vol. 108, suppl 1, pp. 4615-4622. doi: 10.1073/pnas.1000082107.

Banati M., Csecsei P., Koszegi E. et al. Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system. European journal of neurology, 2013, vol. 20, no. 11, pp. 1492-1495. doi: 10.1111/ene.12072.

Ezendam J., de Klerk A., Gremmer E.R., van Loveren H. Effects of Bifidobacterium animalis administered during lactation on allergic and autoimmune responses in rodents. Clinical and experimental immunology, 2008, vol. 154, no. 3, pp. 424-431. doi: 10.1111/j.1365-2249.2008.03788.x.

Ezendam J., van Loveren H. Lactobacillus casei Shirota administered during lactation increases the duration of autoimmunity in rats and enhances lung inflammation in mice. The British journal of nutrition, 2008, vol. 99, no. 1, pp. 83-90. doi: 10.1017/S0007114507803412.

Maassen C.B., Claassen E. Strain-dependent effects of probiotic lactobacilli on EAE autoimmunity. Vaccine, 2008, vol. 26, pp. 2056-2057. doi: 10.1016/j.vaccine.2008.02.035.

Kobayashi T., Suzuki T., Kaji R. et al. Probiotic upregulation of peripheral IL-17 responses does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis mouse models. Immunopharmacology and immunotoxicology, 2012, vol. 34, no. 3, pp. 423-433. doi: 10.3109/08923973.2010.617755.

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. Clinical immunology (Orlando, Fla), 2013, vol. 146, no. 3, pp. 217-227. doi: 10.1016/j.clim.2013.01.001.

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, vol. 5, no. 2, e9009. doi: 10.1371/journal.pone.0009009.

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, vol. 6, no. 11, e27644. doi: 10.1371/journal.pone.0027644.

Rezende R.M., Oliveira R.P., Medeiros S.R. et al. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells. Journal of autoimmunity, 2013, vol. 40, pp. 45-57. doi: 10.1016/j.jaut.2012.07.012.

Kusu T., Kayama H., Kinoshita M. et al. Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine. Journal of immunology, 2013, vol. 190, no. 2, pp. 774-783. doi: 10.4049/jimmunol.1103067.

Kleinewietfeld M., Manzel A., Titze J. et al. Sodiumchloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature, 2013, vol. 496, pp. 518-522. doi: 10.1038/nature11868.

Varrin-Doyer M., Spencer C.M., Schulze-Topphoff U. et al. Aquaporin 4-Specific T Cells in Neuromyelitis Optica Exhibit a Th17 Bias and Recognize Clostridium ABC Transporter. Annals of neurology, 2012, vol. 72, no. 1, pp. 53-64. doi: 10.1002/ana.23651.

Maes M., Twisk F.N., Kubera M. et al. Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome. Journal of affective disorders, 2012, vol. 136, no. 3, pp. 909-917. doi: 10.1016/j.jad.2011.09.010.

Gilbert K., Arseneault-Breard J., Flores Monaco F. et al. Attenuation of post-myocardial infarction depression in rats by n-3 fatty acids or probiotics starting after the onset of reperfusion. The British journal of nutrition, 2013, vol. 109, no. 1, pp. 50-56. doi: 10.1017/S0007114512003807.

Chiu I.M., Heesters B.A., Ghasemlou N. et al. Bacteria activate sensory neurons that modulate pain and inflammation. Nature, 2013, vol. 501, pp. 52-57. doi: 10.1038/nature12479.