Microbiome-The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health

Karolina Skonieczna-Żydecka, Wojciech Marlicz, Agata Misera, Anastasios Koulaouzidis, Igor Łoniewski, Karolina Skonieczna-Żydecka, Wojciech Marlicz, Agata Misera, Anastasios Koulaouzidis, Igor Łoniewski

Abstract

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine, and immunological mechanisms. There is mounting data that gut microbiota is the source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity. Most GI diseases are associated with altered transmission within the GBA that are influenced by both genetic and environmental factors. Current treatment protocols for GI and non-GI disorders may positively or adversely affect the composition of intestinal microbiota with a diverse impact on therapeutic outcome(s). Alterations of gut microbiota have been associated with mood and depressive disorders. Moreover, mental health is frequently affected in GI and non-GI diseases. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example, next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Elucidating the role of stem cell⁻host microbiome cross talks in tissues in GBA disorders might lead to the development of next generation diagnostics and therapeutics. Psychobiotics are a new class of beneficial bacteria with documented efficacy for the treatment of GBA disorders. Novel therapies interfering with small molecules involved in adult stem cell trafficking are on the horizon.

Keywords: adult stem cells; functional gastrointestinal disorders; gut brain axis; inflammatory bowel disease (IBD); microbiota.

Conflict of interest statement

Igor Łoniewski and Wojciech Marlicz are cofounders and shareholders in the Sanprobi-probiotic manufacturer and marketing company. Karolina Skonieczna-Żydecka received remunerations for speaking engagements from Sanprobi. The content of this study was neither influenced nor constrained by these facts. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The bidirectional signaling within the GBA with the involvement of sterile inflammation of the brain and actions of microbiota and circulating adult stem cells. For details, see the text.

References

    1. World Health Organization Mental Health Included in the UN Sustainable Development Goals. [(accessed on 25 November 2018)]; Available online:
    1. World Health Organization Third United Nations High-level Meeting on NCDs. [(accessed on 25 November 2018)]; Available online:
    1. Chandra P.S., Chand P. Towards a new era for mental health. Lancet. 2018 doi: 10.1016/S0140-6736(18)32272-4.
    1. Patel V., Saxena S., Lund C., Thornicroft G., Baingana F., Bolton P., Chisholm D., Collins P.Y., Cooper J.L., Eaton J., et al. The Lancet Commission on global mental health and sustainable development. Lancet. 2018 doi: 10.1016/S0140-6736(18)31612-X.
    1. Gallagher J. More than Half Your Body is not Human. [(accessed on 6 December 2018)]; Available online: .
    1. Lynch S.V., Pedersen O. The Human Intestinal Microbiome in Health and Disease. N. Engl. J. Med. 2016;375:2369–2379. doi: 10.1056/NEJMra1600266.
    1. Bloomfield S.F., Rook G.A., Scott E.A., Shanahan F., Stanwell-Smith R., Turner P. Time to abandon the hygiene hypothesis: New perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene. Perspect. Public Health. 2016;136:213–224. doi: 10.1177/1757913916650225.
    1. Bello M.G.D., Knight R., Gilbert J.A., Blaser M.J. Preserving microbial diversity. Science. 2018;362:33–34. doi: 10.1126/science.aau8816.
    1. Bretin A., Gewirtz A.T., Chassaing B. Microbiota and metabolism: What’s new in 2018? Am. J. Physiol. Endocrinol. Metab. 2018;315:1–6. doi: 10.1152/ajpendo.00014.2018.
    1. Rea D., Coppola G., Palma G., Barbieri A., Luciano A., Del Prete P., Rossetti S., Berretta M., Facchini G., Perdonà S., et al. Microbiota effects on cancer: From risks to therapies. Oncotarget. 2018;9:17915–17927. doi: 10.18632/oncotarget.24681.
    1. Chu H., Williams B., Schnabl B. Gut microbiota, fatty liver disease, and hepatocellular carcinoma. Liver Res. 2018;2:43–51. doi: 10.1016/j.livres.2017.11.005.
    1. Marlicz W., Yung D.E., Skonieczna-Żydecka K., Loniewski I., van Hemert S., Loniewska B., Koulaouzidis A. From clinical uncertainties to precision medicine: The emerging role of the gut barrier and microbiome in small bowel functional diseases. Expert Rev. Gastroenterol. Hepatol. 2017;11:961–978. doi: 10.1080/17474124.2017.1343664.
    1. Sanduzzi Zamparelli M., Compare D., Coccoli P., Rocco A., Nardone O.M., Marrone G., Gasbarrini A., Grieco A., Nardone G., Miele L. The metabolic role of gut microbiota in the development of nonalcoholic fatty liver disease and cardiovascular disease. Int. J. Mol. Sci. 2016;17:1225. doi: 10.3390/ijms17081225.
    1. Skonieczna-Żydecka K., Łoniewski I., Maciejewska D., Marlicz W. Mikrobiota jelitowa iskładniki pokarmowe jako determinanty funkcji układu nerwowego. Część I. Mikrobiota przewodu pokarmowego. Aktualności Neurologiczne. 2017;17:181–188. doi: 10.15557/AN.2017.0020. (In Polish)
    1. Cenit M.C., Sanz Y., Codoñer-Franch P. Influence of gut microbiota on neuropsychiatric disorders. World J. Gastroenterol. 2017;23:5486–5498. doi: 10.3748/wjg.v23.i30.5486.
    1. Marizzoni M., Provasi S., Cattaneo A., Frisoni G.B. Microbiota and neurodegenerative diseases. Curr. Opin. Neurol. 2017;30:630–638. doi: 10.1097/WCO.0000000000000496.
    1. Stasi C., Nisita C., Cortopassi S., Corretti G., Gambaccini D., De Bortoli N., Fani B., Simonetti N., Ricchiuti A., Dell’Osso L., et al. Subthreshold psychiatric psychopathology in functional gastrointestinal disorders: Can it be the bridge between gastroenterology and psychiatry? Gastroenterol. Res. Pract. 2017;2017 doi: 10.1155/2017/1953435.
    1. Bernstein C.N., Hitchon C.A., Walld R., Bolton J.M., Sareen J., Walker J.R., Graff L.A., Patten S.B., Singer A., Lix L.M., et al. Increased burden of psychiatric disorders in inflammatory bowel disease. Inflamm. Bowel Dis. 2018 doi: 10.1093/ibd/izy235.
    1. Chan W., Shim H.H., Lim M.S., Sawadjaan F.L.B., Isaac S.P., Chuah S.W., Leong R., Kong C. Symptoms of anxiety and depression are independently associated with inflammatory bowel disease-related disability. Dig. Liver Dis. 2017;49:1314–1319. doi: 10.1016/j.dld.2017.08.020.
    1. Frolkis A.D., Vallerand I.A., Shaheen A.-A., Lowerison M.W., Swain M.G., Barnabe C., Patten S.B., Kaplan G.G. Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression. Gut. 2018 doi: 10.1136/gutjnl-2018-317182.
    1. Drossman D.A., Hasler W.L. Rome IV-functional GI disorders: Disorders of gut-brain interaction. Gastroenterology. 2016;150:1257–1261. doi: 10.1053/j.gastro.2016.03.035.
    1. Zhong L., Shanahan E.R., Raj A., Koloski N.A., Fletcher L., Morrison M., Walker M.M., Talley N.J., Holtmann G. Dyspepsia and the microbiome: Time to focus on the small intestine. Gut. 2017;66:1168–1169. doi: 10.1136/gutjnl-2016-312574.
    1. Vanheel H., Vicario M., Vanuytsel T., Van Oudenhove L., Martinez C., Keita Å.V., Pardon N., Santos J., Söderholm J.D., Tack J., et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut. 2014;63:262–271. doi: 10.1136/gutjnl-2012-303857.
    1. Giamarellos-Bourboulis E., Tang J., Pyleris E., Pistiki A., Barbatzas C., Brown J., Lee C.C., Harkins T.T., Kim G., Weitsman S., et al. Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome. Scand. J. Gastroenterol. 2015;50:1076–1087. doi: 10.3109/00365521.2015.1027261.
    1. Martínez C., Lobo B., Pigrau M., Ramos L., González-Castro A.M., Alonso C., Guilarte M., Guilá M., de Torres I., Azpiroz F., et al. Diarrhoea-predominant irritable bowel syndrome: An organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut. 2013;62:1160–1168. doi: 10.1136/gutjnl-2012-302093.
    1. Barbara G., Wang B., Stanghellini V., de Giorgio R., Cremon C., Di Nardo G., Trevisani M., Campi B., Geppetti P., Tonini M., et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology. 2007;132:26–37. doi: 10.1053/j.gastro.2006.11.039.
    1. Shah E., Rezaie A., Riddle M., Pimentel M. Psychological disorders in gastrointestinal disease: Epiphenomenon, cause or consequence? Ann. Gastroenterol. 2014;27:224–230.
    1. Gastrointestinal Symptoms in Psychiatry: Comparison of Direct Applications and Referrals. [(accessed on 19 November 2018)]; Available online: .
    1. Wilder-Smith C.H., Olesen S.S., Materna A., Drewes A.M. Fermentable sugar ingestion, gas production, and gastrointestinal and central nervous system symptoms in patients with functional disorders. Gastroenterology. 2018;155:1034–1044. doi: 10.1053/j.gastro.2018.07.013.
    1. Codagnone M.G., Spichak S., O’Mahony S.M., O’Leary O.F., Clarke G., Stanton C., Dinan T.G., Cryan J.F. Programming bugs: Microbiota and the developmental origins of brain health and disease. Biol. Psychiatry. 2018 doi: 10.1016/j.biopsych.2018.06.014.
    1. Luczynski P., Whelan S.O., O’Sullivan C., Clarke G., Shanahan F., Dinan T.G., Cryan J.F. Adult microbiota-deficient mice have distinct dendritic morphological changes: Differential effects in the amygdala and hippocampus. Eur. J. Neurosci. 2016;44:2654–2666. doi: 10.1111/ejn.13291.
    1. Hoban A.E., Stilling R.M., Ryan F.J., Shanahan F., Dinan T.G., Claesson M.J., Clarke G., Cryan J.F. Regulation of prefrontal cortex myelination by the microbiota. Transl. Psychiatry. 2016;6:774. doi: 10.1038/tp.2016.42.
    1. Lu J., Lu L., Yu Y., Cluette-Brown J., Martin C.R., Claud E.C. Effects of intestinal microbiota on brain development in humanized gnotobiotic mice. Sci. Rep. 2018;8:5443. doi: 10.1038/s41598-018-23692-w.
    1. Desbonnet L., Clarke G., Shanahan F., Dinan T.G., Cryan J.F. Microbiota is essential for social development in the mouse. Mol. Psychiatry. 2014;19:146–148. doi: 10.1038/mp.2013.65.
    1. Marlicz W., Poniewierska-Baran A., Rzeszotek S., Bartoszewski R., Skonieczna-Żydecka K., Starzyńska T., Ratajczak M.Z. A novel potential role of pituitary gonadotropins in the pathogenesis of human colorectal cancer. PLoS ONE. 2018;13:e0189337. doi: 10.1371/journal.pone.0189337.
    1. Kaelberer M.M., Buchanan K.L., Klein M.E., Barth B.B., Montoya M.M., Shen X., Bohórquez D.V. A gut-brain neural circuit for nutrient sensory transduction. Science. 2018;361 doi: 10.1126/science.aat5236.
    1. Paolicelli R.C., Bergamini G., Rajendran L. Cell-to-cell communication by extracellular vesicles: Focus on microglia. Neuroscience. 2018 doi: 10.1016/j.neuroscience.2018.04.003.
    1. Kavvadia M., Santis G.L.D., Cascapera S., Lorenzo A.D. Psychobiotics as integrative therapy for neuropsychiatric disorders with special emphasis on the microbiota-gut-brain axis. Biomed. Prev. 2017;2:8. doi: 10.19252/00000006F.
    1. Riboni F.V., Belzung C. Stress and psychiatric disorders: From categorical to dimensional approaches. Curr. Opin. Behav. Sci. 2017;14:72–77. doi: 10.1016/j.cobeha.2016.12.011.
    1. Sudo N., Chida Y., Aiba Y., Sonoda J., Oyama N., Yu X.-N., Kubo C., Koga Y. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. (Lond.) 2004;558:263–275. doi: 10.1113/jphysiol.2004.063388.
    1. Crumeyrolle-Arias M., Jaglin M., Bruneau A., Vancassel S., Cardona A., Daugé V., Naudon L., Rabot S. Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology. 2014;42:207–217. doi: 10.1016/j.psyneuen.2014.01.014.
    1. König J., Wells J., Cani P.D., García-Ródenas C.L., MacDonald T., Mercenier A., Whyte J., Troost F., Brummer R.-J. Human intestinal barrier function in health and disease. Clin. Transl. Gastroenterol. 2016;7:196. doi: 10.1038/ctg.2016.54.
    1. Fond G., Boukouaci W., Chevalier G., Regnault A., Eberl G., Hamdani N., Dickerson F., Macgregor A., Boyer L., Dargel A., et al. The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic review. Pathol. Biol. 2015;63:35–42. doi: 10.1016/j.patbio.2014.10.003.
    1. Spadoni I., Zagato E., Bertocchi A., Paolinelli R., Hot E., Di Sabatino A., Caprioli F., Bottiglieri L., Oldani A., Viale G., et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science. 2015;350:830–834. doi: 10.1126/science.aad0135.
    1. Brown E.M., Sadarangani M., Finlay B.B. The role of the immune system in governing host-microbe interactions in the intestine. Nat. Immunol. 2013;14:660–667. doi: 10.1038/ni.2611.
    1. Groschwitz K.R., Hogan S.P. Intestinal barrier function: Molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol. 2009;124:3–20. doi: 10.1016/j.jaci.2009.05.038.
    1. Tripathi A., Lammers K.M., Goldblum S., Shea-Donohue T., Netzel-Arnett S., Buzza M.S., Antalis T.M., Vogel S.N., Zhao A., Yang S., et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc. Natl. Acad. Sci. USA. 2009;106:16799–16804. doi: 10.1073/pnas.0906773106.
    1. Fasano A. Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity, and cancer. Physiol. Rev. 2011;91:151–175. doi: 10.1152/physrev.00003.2008.
    1. Sharon G., Sampson T.R., Geschwind D.H., Mazmanian S.K. The central nervous system and the gut microbiome. Cell. 2016;167:915–932. doi: 10.1016/j.cell.2016.10.027.
    1. Al-Asmakh M., Anuar F., Zadjali F., Rafter J., Pettersson S. Gut microbial communities modulating brain development and function. Gut Microbes. 2012;3:366–373. doi: 10.4161/gmic.21287.
    1. Daneman R., Rescigno M. The gut immune barrier and the blood-brain barrier: Are they so different? Immunity. 2009;31:722–735. doi: 10.1016/j.immuni.2009.09.012.
    1. Mayer E.A., Craske M., Naliboff B.D. Depression, anxiety, and the gastrointestinal system. J. Clin. Psychiatry. 2001;62(Suppl. 8):28–37.
    1. Carding S., Verbeke K., Vipond D.T., Corfe B.M., Owen L.J. Dysbiosis of the gut microbiota in disease. Microb. Ecol. Health Dis. 2015;26:26191. doi: 10.3402/mehd.v26.26191.
    1. Rothschild D., Weissbrod O., Barkan E., Kurilshikov A., Korem T., Zeevi D., Costea P.I., Godneva A., Kalka I.N., Bar N., et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555:210–215. doi: 10.1038/nature25973.
    1. Foster J.A., Neufeld K.-A.M. Gut-brain axis: How the microbiome influences anxiety and depression. Trends Neurosci. 2013;36:305–312. doi: 10.1016/j.tins.2013.01.005.
    1. Sherwin E., Dinan T.G., Cryan J.F. Recent developments in understanding the role of the gut microbiota in brain health and disease. Ann. N. Y. Acad. Sci. 2018;1420:5–25. doi: 10.1111/nyas.13416.
    1. Rogers G.B., Keating D.J., Young R.L., Wong M.-L., Licinio J., Wesselingh S. From gut dysbiosis to altered brain function and mental illness: Mechanisms and pathways. Mol. Psychiatry. 2016;21:738–748. doi: 10.1038/mp.2016.50.
    1. Bastiaanssen T.F.S., Cowan C.S.M., Claesson M.J., Dinan T.G., Cryan J.F. Making sense of … the microbiome in psychiatry. Int. J. Neuropsychopharmacol. 2018 doi: 10.1093/ijnp/pyy067.
    1. Grochowska M., Wojnar M., Radkowski M. The gut microbiota in neuropsychiatric disorders. Acta Neurobiol. Exp. 2018;78:69–81. doi: 10.21307/ane-2018-008.
    1. Aizawa E., Tsuji H., Asahara T., Takahashi T., Teraishi T., Yoshida S., Ota M., Koga N., Hattori K., Kunugi H. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J. Affect. Disord. 2016;202:254–257. doi: 10.1016/j.jad.2016.05.038.
    1. Jiang H., Ling Z., Zhang Y., Mao H., Ma Z., Yin Y., Wang W., Tang W., Tan Z., Shi J., et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav. Immun. 2015;48:186–194. doi: 10.1016/j.bbi.2015.03.016.
    1. Szczesniak O., Hestad K.A., Hanssen J.F., Rudi K. Isovaleric acid in stool correlates with human depression. Nutr. Neurosci. 2016;19:279–283. doi: 10.1179/1476830515Y.0000000007.
    1. Ogyu K., Kubo K., Noda Y., Iwata Y., Tsugawa S., Omura Y., Wada M., Tarumi R., Plitman E., Moriguchi S., et al. Kynurenine pathway in depression: A systematic review and meta-analysis. Neurosci. Biobehav. Rev. 2018;90:16–25. doi: 10.1016/j.neubiorev.2018.03.023.
    1. Schwarz E., Maukonen J., Hyytiäinen T., Kieseppä T., Orešič M., Sabunciyan S., Mantere O., Saarela M., Yolken R., Suvisaari J. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophr. Res. 2018;192:398–403. doi: 10.1016/j.schres.2017.04.017.
    1. Shen Y., Xu J., Li Z., Huang Y., Yuan Y., Wang J., Zhang M., Hu S., Liang Y. Analysis of gut microbiota diversity and auxiliary diagnosis as a biomarker in patients with schizophrenia: A cross-sectional study. Schizophr. Res. 2018 doi: 10.1016/j.schres.2018.01.002.
    1. Evans S.J., Bassis C.M., Hein R., Assari S., Flowers S.A., Kelly M.B., Young V.B., Ellingrod V.E., McInnis M.G. The gut microbiome composition associates with bipolar disorder and illness severity. J. Psychiatr. Res. 2017;87:23–29. doi: 10.1016/j.jpsychires.2016.12.007.
    1. Painold A., Mörkl S., Kashofer K., Halwachs B., Dalkner N., Bengesser S., Birner A., Fellendorf F., Platzer M., Queissner R., et al. A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode. Bipolar Disord. 2018 doi: 10.1111/bdi.12682.
    1. Keshavarzian A., Green S.J., Engen P.A., Voigt R.M., Naqib A., Forsyth C.B., Mutlu E., Shannon K.M. Colonic bacterial composition in Parkinson’s disease. Mov. Disord. 2015;30:1351–1360. doi: 10.1002/mds.26307.
    1. De Angelis M., Francavilla R., Piccolo M., De Giacomo A., Gobbetti M. Autism spectrum disorders and intestinal microbiota. Gut Microbes. 2015;6:207–213. doi: 10.1080/19490976.2015.1035855.
    1. Kushak R.I., Winter H.S., Buie T.M., Cox S.B., Phillips C.D., Ward N.L. Analysis of the Duodenal Microbiome in Autistic Individuals: Association With Carbohydrate Digestion. J. Pediatr. Gastroenterol. Nutr. 2017;64:110–116. doi: 10.1097/MPG.0000000000001458.
    1. Lee Y., Park J.-Y., Lee E.-H., Yang J., Jeong B.-R., Kim Y.-K., Seoh J.-Y., Lee S., Han P.-L., Kim E.-J. Rapid assessment of microbiota changes in individuals with autism spectrum disorder using bacteria-derived membrane vesicles in urine. Exp. Neurobiol. 2017;26:307–317. doi: 10.5607/en.2017.26.5.307.
    1. Strati F., Cavalieri D., Albanese D., De Felice C., Donati C., Hayek J., Jousson O., Leoncini S., Renzi D., Calabrò A., et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 2017;5:24. doi: 10.1186/s40168-017-0242-1.
    1. Bryn V., Verkerk R., Skjeldal O.H., Saugstad O.D., Ormstad H. Kynurenine pathway in autism spectrum disorders in children. Neuropsychobiology. 2017;76:82–88. doi: 10.1159/000488157.
    1. Aarts E., Ederveen T.H.A., Naaijen J., Zwiers M.P., Boekhorst J., Timmerman H.M., Smeekens S.P., Netea M.G., Buitelaar J.K., Franke B., et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS ONE. 2017;12:e0183509. doi: 10.1371/journal.pone.0183509.
    1. Cattaneo A., Cattane N., Galluzzi S., Provasi S., Lopizzo N., Festari C., Ferrari C., Guerra U.P., Paghera B., Muscio C., et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol. Aging. 2017;49:60–68. doi: 10.1016/j.neurobiolaging.2016.08.019.
    1. 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., Blennow K., et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017;7:13537. doi: 10.1038/s41598-017-13601-y.
    1. Cekanaviciute E., Yoo B.B., Runia T.F., Debelius J.W., Singh S., Nelson C.A., Kanner R., Bencosme Y., Lee Y.K., Hauser S.L., et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl. Acad. Sci. USA. 2017;114:10713–10718. doi: 10.1073/pnas.1711235114.
    1. Schwensen H.F., Kan C., Treasure J., Høiby N., Sjögren M. A systematic review of studies on the faecal microbiota in anorexia nervosa: Future research may need to include microbiota from the small intestine. Eat. Weight Disord. 2018;23:399–418. doi: 10.1007/s40519-018-0499-9.
    1. Bailey M.T., Dowd S.E., Galley J.D., Hufnagle A.R., Allen R.G., Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation. Brain Behav. Immun. 2011;25:397–407. doi: 10.1016/j.bbi.2010.10.023.
    1. Zijlmans M.A.C., Korpela K., Riksen-Walraven J.M., de Vos W.M., de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015;53:233–245. doi: 10.1016/j.psyneuen.2015.01.006.
    1. Yarandi S.S., Peterson D.A., Treisman G.J., Moran T.H., Pasricha P.J. modulatory effects of gut microbiota on the central nervous system: how gut could play a role in neuropsychiatric health and diseases. J. Neurogastroenterol. Motil. 2016;22:201–212. doi: 10.5056/jnm15146.
    1. Kelly J.R., Kennedy P.J., Cryan J.F., Dinan T.G., Clarke G., Hyland N.P. Breaking down the barriers: The gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci. 2015;9:392. doi: 10.3389/fncel.2015.00392.
    1. Ait-Belgnaoui A., Bradesi S., Fioramonti J., Theodorou V., Bueno L. Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: Role of myosin light chain kinase. Pain. 2005;113:141–147. doi: 10.1016/j.pain.2004.10.002.
    1. Winter G., Hart R.A., Charlesworth R.P.G., Sharpley C.F. Gut microbiome and depression: What we know and what we need to know. Rev. Neurosci. 2018;29:629–643. doi: 10.1515/revneuro-2017-0072.
    1. Bauer M.E., Teixeira A.L. Inflammation in psychiatric disorders: What comes first? Ann. N. Y. Acad. Sci. 2018 doi: 10.1111/nyas.13712.
    1. Spiller R., Lam C. An Update on Post-infectious Irritable Bowel Syndrome: Role of Genetics, Immune Activation, Serotonin and Altered Microbiome. J. Neurogastroenterol. Motil. 2012;18:258–268. doi: 10.5056/jnm.2012.18.3.258.
    1. Futagami S., Itoh T., Sakamoto C. Systematic review with meta-analysis: Post-infectious functional dyspepsia. Aliment. Pharmacol. Ther. 2015;41:177–188. doi: 10.1111/apt.13006.
    1. Neuendorf R., Harding A., Stello N., Hanes D., Wahbeh H. Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review. J. Psychosom. Res. 2016;87:70–80. doi: 10.1016/j.jpsychores.2016.06.001.
    1. Ratajczak M.Z., Pedziwiatr D., Cymer M., Kucia M., Kucharska-Mazur J., Samochowiec J. Sterile inflammation of brain, due to activation of innate immunity, as a culprit in psychiatric disorders. Front. Psychiatry. 2018;9 doi: 10.3389/fpsyt.2018.00060.
    1. Kahn M. Wnt signaling in stem cells and cancer stem cells: A tale of two coactivators. Prog. Mol. Biol. Transl. Sci. 2018;153:209–244. doi: 10.1016/bs.pmbts.2017.11.007.
    1. Kabiri Z., Greicius G., Zaribafzadeh H., Hemmerich A., Counter C.M., Virshup D.M. Wnt signaling suppresses MAPK-driven proliferation of intestinal stem cells. J. Clin. Invest. 2018;128:3806–3812. doi: 10.1172/JCI99325.
    1. Xing L., Anbarchian T., Tsai J.M., Plant G.W., Nusse R. Wnt/β-catenin signaling regulates ependymal cell development and adult homeostasis. Proc. Natl. Acad. Sci. USA. 2018;115:5954–5962. doi: 10.1073/pnas.1803297115.
    1. Ratajczak M.Z., Liu R., Marlicz W., Blogowski W., Starzynska T., Wojakowski W., Zuba-Surma E. Identification of very small embryonic/epiblast-like stem cells (VSELs) circulating in peripheral blood during organ/tissue injuries. Methods Cell. Biol. 2011;103:31–54. doi: 10.1016/B978-0-12-385493-3.00003-6.
    1. Wojakowski W., Tendera M., Kucia M., Zuba-Surma E., Paczkowska E., Ciosek J., Hałasa M., Król M., Kazmierski M., Buszman P., et al. Mobilization of bone marrow-derived Oct-4+ SSEA-4+ very small embryonic-like stem cells in patients with acute myocardial infarction. J. Am. Coll. Cardiol. 2009;53:1–9. doi: 10.1016/j.jacc.2008.09.029.
    1. Paczkowska E., Kucia M., Koziarska D., Halasa M., Safranow K., Masiuk M., Karbicka A., Nowik M., Nowacki P., Ratajczak M.Z., et al. Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke. Stroke. 2009;40:1237–1244. doi: 10.1161/STROKEAHA.108.535062.
    1. Drukała J., Paczkowska E., Kucia M., Młyńska E., Krajewski A., Machaliński B., Madeja Z., Ratajczak M.Z. Stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients after skin burn injury. Stem Cell. Rev. 2012;8:184–194. doi: 10.1007/s12015-011-9272-4.
    1. Marlicz W., Zuba-Surma E., Kucia M., Blogowski W., Starzynska T., Ratajczak M.Z. Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn’s disease. Inflamm. Bowel Dis. 2012;18:1711–1722. doi: 10.1002/ibd.22875.
    1. Stonesifer C., Corey S., Ghanekar S., Diamandis Z., Acosta S.A., Borlongan C.V. Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms. Prog. Neurobiol. 2017;158:94–131. doi: 10.1016/j.pneurobio.2017.07.004.
    1. Ratajczak J., Zuba-Surma E., Paczkowska E., Kucia M., Nowacki P., Ratajczak M.Z. Stem cells for neural regeneration—A potential application of very small embryonic-like stem cells. J. Physiol. Pharmacol. 2011;62:3–12.
    1. Kim C., Schneider G., Abdel-Latif A., Mierzejewska K., Sunkara M., Borkowska S., Ratajczak J., Morris A.J., Kucia M., Ratajczak M.Z. Ceramide-1-phosphate regulates migration of multipotent stromal cells and endothelial progenitor cells--implications for tissue regeneration. Stem Cells. 2013;31:500–510. doi: 10.1002/stem.1291.
    1. Jabłoński M., Mazur J.K., Tarnowski M., Dołęgowska B., Pędziwiatr D., Kubiś E., Budkowska M., Sałata D., Wysiecka J.P., Kazimierczak A., et al. Mobilization of peripheral blood stem cells and changes in the concentration of plasma factors influencing their movement in patients with panic disorder. Stem Cell. Rev. 2017;13:217–225. doi: 10.1007/s12015-016-9700-6.
    1. Adamiak M., Bujko K., Cymer M., Plonka M., Glaser T., Kucia M., Ratajczak J., Ulrich H., Abdel-Latif A., Ratajczak M.Z. Novel evidence that extracellular nucleotides and purinergic signaling induce innate immunity-mediated mobilization of hematopoietic stem/progenitor cells. Leukemia. 2018;32:1920–1931. doi: 10.1038/s41375-018-0122-0.
    1. Ratajczak M.Z., Kim C., Ratajczak J., Janowska-Wieczorek A. Innate immunity as orchestrator of bone marrow homing for hematopoietic stem/progenitor cells. Adv. Exp. Med. Biol. 2013;735:219–232.
    1. Ratajczak M.Z., Ratajczak J. extracellular microvesicles as game changers in better understanding the complexity of cellular interactions-from bench to clinical applications. Am. J. Med. Sci. 2017;354:449–452. doi: 10.1016/j.amjms.2017.06.001.
    1. Kucharska-Mazur J., Tarnowski M., Dołęgowska B., Budkowska M., Pędziwiatr D., Jabłoński M., Pełka-Wysiecka J., Kazimierczak A., Ratajczak M.Z., Samochowiec J. Novel evidence for enhanced stem cell trafficking in antipsychotic-naïve subjects during their first psychotic episode. J. Psychiatr. Res. 2014;49:18–24. doi: 10.1016/j.jpsychires.2013.10.016.
    1. Hunter S.F., Bowen J.D., Reder A.T. The direct effects of fingolimod in the central nervous system: Implications for relapsing multiple sclerosis. CNS Drugs. 2016;30:135–147. doi: 10.1007/s40263-015-0297-0.
    1. Mutneja H.R., Arora S., Vij A. Ozanimod treatment for ulcerative colitis. N. Engl. J. Med. 2016;375:e17. doi: 10.1056/NEJMc1607287.
    1. Szulińska M., Łoniewski I., van Hemert S., Sobieska M., Bogdański P. Dose-dependent effects of multispecies probiotic supplementation on the lipopolysaccharide (LPS) level and cardiometabolic profile in obese postmenopausal women: A 12-week randomized clinical trial. Nutrients. 2018;10:773. doi: 10.3390/nu10060773.
    1. Marlicz W., Loniewski I., Grimes D.S., Quigley E.M. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: Contrasting interactions in the stomach and small intestine. Mayo Clin. Proc. 2014;89:1699–1709. doi: 10.1016/j.mayocp.2014.07.015.
    1. Le Bastard Q., Al-Ghalith G.A., Grégoire M., Chapelet G., Javaudin F., Dailly E., Batard E., Knights D., Montassier E. Systematic review: Human gut dysbiosis induced by non-antibiotic prescription medications. Aliment. Pharmacol. Ther. 2018;47:332–345. doi: 10.1111/apt.14451.
    1. Utzeri E., Usai P. Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease. World J. Gastroenterol. 2017;23:3954–3963. doi: 10.3748/wjg.v23.i22.3954.
    1. Wallace J.L., Syer S., Denou E., de Palma G., Vong L., McKnight W., Jury J., Bolla M., Bercik P., Collins S.M., et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology. 2011;141 doi: 10.1053/j.gastro.2011.06.075.
    1. Maier L., Pruteanu M., Kuhn M., Zeller G., Telzerow A., Anderson E.E., Brochado A.R., Fernandez K.C., Dose H., Mori H., et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555:623–628. doi: 10.1038/nature25979.
    1. Koliada A., Syzenko G., Moseiko V., Budovska L., Puchkov K., Perederiy V., Gavalko Y., Dorofeyev A., Romanenko M., Tkach S., et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol. 2017;17 doi: 10.1186/s12866-017-1027-1.
    1. Davey K.J., O’Mahony S.M., Schellekens H., O’Sullivan O., Bienenstock J., Cotter P.D., Dinan T.G., Cryan J.F. Gender-dependent consequences of chronic olanzapine in the rat: Effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berl.) 2012;221:155–169. doi: 10.1007/s00213-011-2555-2.
    1. Davey K.J., Cotter P.D., O’Sullivan O., Crispie F., Dinan T.G., Cryan J.F., O’Mahony S.M. Antipsychotics and the gut microbiome: Olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl. Psychiatry. 2013;3:309. doi: 10.1038/tp.2013.83.
    1. Bahr S.M., Weidemann B.J., Castro A.N., Walsh J.W., deLeon O., Burnett C.M.L., Pearson N.A., Murry D.J., Grobe J.L., Kirby J.R. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure. EBioMedicine. 2015;2:1725–1734. doi: 10.1016/j.ebiom.2015.10.018.
    1. Morgan A.P., Crowley J.J., Nonneman R.J., Quackenbush C.R., Miller C.N., Ryan A.K., Bogue M.A., Paredes S.H., Yourstone S., Carroll I.M., et al. The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse. PLoS ONE. 2014;9:e115225. doi: 10.1371/journal.pone.0115225.
    1. Castaner O., Goday A., Park Y.-M., Lee S.-H., Magkos F., Shiow S.-A.T.E., Schröder H. The Gut Microbiome Profile in Obesity: A Systematic Review. [(accessed on 8 October 2018)]; Available online:
    1. Bahr S.M., Tyler B.C., Wooldridge N., Butcher B.D., Burns T.L., Teesch L.M., Oltman C.L., Azcarate-Peril M.A., Kirby J.R., Calarge C.A. Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children. Transl. Psychiatry. 2015;5:652. doi: 10.1038/tp.2015.135.
    1. Flowers S.A., Evans S.J., Ward K.M., McInnis M.G., Ellingrod V.L. Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort. Pharmacotherapy. 2017;37:261–267. doi: 10.1002/phar.1890.
    1. Yuan X., Zhang P., Wang Y., Liu Y., Li X., Kumar B.U., Hei G., Lv L., Huang X.-F., Fan X., et al. Changes in metabolism and microbiota after 24-week risperidone treatment in drug naïve, normal weight patients with first episode schizophrenia. Schizophr. Res. 2018 doi: 10.1016/j.schres.2018.05.017.
    1. Skonieczna-Żydecka K., Łoniewski I., Misera A., Stachowska E., Maciejewska D., Marlicz W., Galling B. Second-generation antipsychotics and metabolism alterations: A systematic review of the role of the gut microbiome. Psychopharmacology. 2018 doi: 10.1007/s00213-018-5102-6.
    1. Lei B., Wei C.J., Tu S.C. Action mechanism of antitubercular isoniazid activation by Mycobacterium tuberculosis KatG, isolation, and characterization of inha inhibitor. J. Biol. Chem. 2000;275:2520–2526. doi: 10.1074/jbc.275.4.2520.
    1. Jena L., Waghmare P., Kashikar S., Kumar S., Harinath B.C. Computational approach to understanding the mechanism of action of isoniazid, an anti-TB drug. Int. J. Mycobacteriol. 2014;3:276–282. doi: 10.1016/j.ijmyco.2014.08.003.
    1. Csiszar K., Molnar J. Mechanism of action of tricyclic drugs on Escherichia coli and Yersinia enterocolitica plasmid maintenance and replication. Anticancer Res. 1992;12:2267–2272.
    1. Binding of Tricyclic Antidepressant Drugs to Trophozoites of Giardia Lamblia. [(accessed on 29 September 2018)]; Available online: .
    1. Antiplasmid Activity of Tricyclic Compounds. [(accessed on 29 September 2018)]; Available online: .
    1. Bitonti A.J., Sjoerdsma A., McCann P.P., Kyle D.E., Oduola A.M., Rossan R.N., Milhous W.K., Davidson D.E. Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine. Science. 1988;242:1301–1303. doi: 10.1126/science.3057629.
    1. Antidepressants Cause Lethal Disruption of Membrane Function in the Human Protozoan Parasite Leishmania. [(accessed on 29 September 2018)]; Available online: .
    1. Munoz-Bellido J.L., Munoz-Criado S., Garcìa-Rodrìguez J.A. Antimicrobial activity of psychotropic drugs: Selective serotonin reuptake inhibitors. Int. J. Antimicrob. Agents. 2000;14:177–180. doi: 10.1016/S0924-8579(99)00154-5.
    1. Ayaz M., Subhan F., Ahmed J., Khan A.-U., Ullah F., Ullah I., Ali G., Syed N.-I.-H., Hussain S. Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance. J. Biol. Res. (Thessalon) 2015;22:4. doi: 10.1186/s40709-015-0028-1.
    1. Coban A.Y., Tanriverdi Cayci Y., Keleş Uludağ S., Durupinar B. Investigation of antibacterial activity of sertralin. Mikrobiyol. Bul. 2009;43:651–656.
    1. Kruszewska H., Zareba T., Tyski S. Examination of antimicrobial activity of selected non-antibiotic medicinal preparations. Acta Pol. Pharm. 2012;69:1368–1371.
    1. Bohnert J.A., Szymaniak-Vits M., Schuster S., Kern W.V. Efflux inhibition by selective serotonin reuptake inhibitors in Escherichia coli. J. Antimicrob. Chemother. 2011;66:2057–2060. doi: 10.1093/jac/dkr258.
    1. Begec Z., Yucel A., Yakupogullari Y., Erdogan M.A., Duman Y., Durmus M., Ersoy M.O. The antimicrobial effects of ketamine combined with propofol: An in vitro study. Braz J. Anesthesiol. 2013;63:461–465. doi: 10.1016/j.bjan.2012.09.003.
    1. Felice V.D., O’Mahony S.M. The microbiome and disorders of the central nervous system. Pharmacol. Biochem. Behav. 2017;160:1–13. doi: 10.1016/j.pbb.2017.06.016.
    1. Mörkl S., Wagner-Skacel J., Lahousen T., Lackner S., Holasek S.J., Bengesser S.A., Painold A., Holl A.K., Reininghaus E. The role of nutrition and the gut-brain axis in psychiatry: A review of the literature. Neuropsychobiology. 2018:1–9. doi: 10.1159/000492834.
    1. Liang S., Wu X., Jin F. Gut-Brain Psychology: Rethinking psychology from the microbiota–gut–brain axis. Front. Integr. Neurosci. 2018;12 doi: 10.3389/fnint.2018.00033.
    1. Tilg H., Schmiderer A., Djanani A. Gut microbiome-immune crosstalk affects progression of cancer. Transl. Gastroenterol. Hepatol. 2018;3 doi: 10.21037/tgh.2018.06.02.
    1. Tilg H., Grander C. Microbiota and diabetes: An increasingly relevant association. Pol. Arch. Int. Med. 2018;128:333–335. doi: 10.20452/pamw.4286.
    1. Adolph T.E., Grander C., Moschen A.R., Tilg H. Liver–microbiome axis in health and disease. Trends Immunol. 2018;39:712–723. doi: 10.1016/j.it.2018.05.002.
    1. Quigley E.M.M. Prebiotics and probiotics in digestive health. Clin. Gastroenterol. Hepatol. 2018 doi: 10.1016/j.cgh.2018.09.028.
    1. WGO Practice Guideline —Probiotics and Prebiotics. [(accessed on 5 October 2018)]; Available online: .
    1. Dinan T.G., Stanton C., Cryan J.F. Psychobiotics: A novel class of psychotropic. Biol. Psychiatry. 2013;74:720–726. doi: 10.1016/j.biopsych.2013.05.001.
    1. Sarkar A., Lehto S.M., Harty S., Dinan T.G., Cryan J.F., Burnet P.W.J. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends Neurosci. 2016;39:763–781. doi: 10.1016/j.tins.2016.09.002.
    1. 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. 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. 2014;11:506–514. doi: 10.1038/nrgastro.2014.66.
    1. Misra S., Mohanty D. Psychobiotics: A new approach for treating mental illness? Crit. Rev. Food Sci. Nutr. 2017:1–7. doi: 10.1080/10408398.2017.1399860.
    1. Ait-Belgnaoui A., Colom A., Braniste V., Ramalho L., Marrot A., Cartier C., Houdeau E., Theodorou V., Tompkins T. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol. Motil. 2014;26:510–520. doi: 10.1111/nmo.12295.
    1. Ait-Belgnaoui A., Payard I., Rolland C., Harkat C., Braniste V., Théodorou V., Tompkins T.A. Bifidobacterium longum and Lactobacillus helveticus synergistically suppress stress-related visceral hypersensitivity through hypothalamic-pituitary-adrenal axis modulation. J. Neurogastroenterol. Motil. 2018;24:138–146. doi: 10.5056/jnm16167.
    1. Gareau M.G., Jury J., MacQueen G., Sherman P.M., Perdue M.H. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut. 2007;56:1522–1528. doi: 10.1136/gut.2006.117176.
    1. Gareau M.G., Wine E., Reardon C., Sherman P.M. Probiotics prevent death caused by citrobacter rodentium infection in neonatal mice. J. Infect. Dis. 2010;201:81–91. doi: 10.1086/648614.
    1. Diop L., Guillou S., Durand H. Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: A double-blind, placebo-controlled, randomized trial. Nutr. Res. 2008;28:1–5. doi: 10.1016/j.nutres.2007.10.001.
    1. Messaoudi M., Lalonde R., Violle N., Javelot H., Desor D., Nejdi A., Bisson J.-F., Rougeot C., Pichelin M., Cazaubiel M., 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;105:755–764. doi: 10.1017/S0007114510004319.
    1. Steenbergen L., Sellaro R., van Hemert S., Bosch J.A., Colzato L.S. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav. Immun. 2015;48:258–264. doi: 10.1016/j.bbi.2015.04.003.
    1. Allen A.P., Hutch W., Borre Y.E., Kennedy P.J., Temko A., Boylan G., Murphy E., Cryan J.F., Dinan T.G., Clarke G. Bifidobacterium longum 1714 as a translational psychobiotic: Modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl. Psychiatry. 2016;6:939. doi: 10.1038/tp.2016.191.
    1. Kato-Kataoka A., Nishida K., Takada M., Kawai M., Kikuchi-Hayakawa H., Suda K., Ishikawa H., Gondo Y., Shimizu K., Matsuki T., et al. 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. 2016;82:3649–3658. doi: 10.1128/AEM.04134-15.
    1. Lv F., Chen S., Wang L., Jiang R., Tian H., Li J., Yao Y., Zhuo C. The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option. Oncotarget. 2017;8:100899–100907. doi: 10.18632/oncotarget.21284.
    1. Huang R., Wang K., Hu J. Effect of probiotics on depression: A systematic review and meta-analysis of randomized controlled trials. Nutrients. 2016;8:483. doi: 10.3390/nu8080483.
    1. McKean J., Naug H., Nikbakht E., Amiet B., Colson N. Probiotics and subclinical psychological symptoms in healthy participants: a systematic review and meta-analysis. J. Altern Complement. Med. 2017;23:249–258. doi: 10.1089/acm.2016.0023.
    1. Ng Q.X., Peters C., Ho C.Y.X., Lim D.Y., Yeo W.-S. A meta-analysis of the use of probiotics to alleviate depressive symptoms. J. Affect. Disord. 2018;228:13–19. doi: 10.1016/j.jad.2017.11.063.
    1. Kazemi A., Noorbala A.A., Azam K., Eskandari M.H., Djafarian K. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clin. Nutr. 2018 doi: 10.1016/j.clnu.2018.04.010.
    1. Reininghaus E.Z., Wetzlmair L.-C., Fellendorf F.T., Platzer M., Queissner R., Birner A., Pilz R., Hamm C., Maget A., Koidl C., et al. The impact of probiotic supplements on cognitive parameters in euthymic individuals with bipolar disorder: A pilot study. Neuropsychobiology. 2018:1–8. doi: 10.1159/000492537.
    1. Citi S. Intestinal barriers protect against disease. Science. 2018;359:1097–1098. doi: 10.1126/science.aat0835.
    1. Zhou L., Foster J.A. Psychobiotics and the gut-brain axis: In the pursuit of happiness. Neuropsychiatr Dis. Treat. 2015;11:715–723. doi: 10.2147/NDT.S61997.
    1. Nishida K., Sawada D., Kawai T., Kuwano Y., Fujiwara S., Rokutan K. Para-psychobiotic Lactobacillus gasseri CP2305 ameliorates stress-related symptoms and sleep quality. J. Appl. Microbiol. 2017;123:1561–1570. doi: 10.1111/jam.13594.
    1. Barichella M., Pacchetti C., Bolliri C., Cassani E., Iorio L., Pusani C., Pinelli G., Privitera G., Cesari I., Faierman S.A., et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT. Neurology. 2016;87:1274–1280. doi: 10.1212/WNL.0000000000003127.
    1. Tamtaji O.R., Taghizadeh M., Daneshvar Kakhaki R., Kouchaki E., Bahmani F., Borzabadi S., Oryan S., Mafi A., Asemi Z. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clin. Nutr. 2018 doi: 10.1016/j.clnu.2018.05.018.
    1. Ticinesi A., Tana C., Nouvenne A., Prati B., Lauretani F., Meschi T. Gut microbiota, cognitive frailty and dementia in older individuals: A systematic review. Clin. Interv. Aging. 2018;13:1497–1511. doi: 10.2147/CIA.S139163.
    1. Agahi A., Hamidi G.A., Daneshvar R., Hamdieh M., Soheili M., Alinaghipour A., Esmaeili Taba S.M., Salami M. Does severity of Alzheimer’s disease contribute to its responsiveness to modifying gut microbiota? A double blind clinical trial. Front. Neurol. 2018;9:662. doi: 10.3389/fneur.2018.00662.
    1. Patusco R., Ziegler J. Role of probiotics in managing gastrointestinal dysfunction in children with autism spectrum disorder: An update for practitioners. Adv. Nutr. 2018;9:637–650. doi: 10.1093/advances/nmy031.
    1. Rudzki L., Ostrowska L., Pawlak D., Małus A., Pawlak K., Waszkiewicz N., Szulc A. Probiotic Lactobacillus plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study. Psychoneuroendocrinology. 2018;100:213–222. doi: 10.1016/j.psyneuen.2018.10.010.

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