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Reviews in the Neurosciences

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Gut microbiome and depression: what we know and what we need to know

Gal Winter / Robert A. Hart / Richard P.G. Charlesworth / Christopher F. Sharpley
Published Online: 2018-02-05 | DOI: https://doi.org/10.1515/revneuro-2017-0072

Abstract

Gut microbiome diversity has been strongly associated with mood-relating behaviours, including major depressive disorder (MDD). This association stems from the recently characterised bi-directional communication system between the gut and the brain, mediated by neuroimmune, neuroendocrine and sensory neural pathways. While the link between gut microbiome and depression is well supported by research, a major question needing to be addressed is the causality in the connection between the two, which will support the understanding of the role that the gut microbiota play in depression. In this article, we address this question by examining a theoretical ‘chronology’, reviewing the evidence supporting two possible sequences of events. First, we discuss that alterations in the gut microbiota populations of specific species might contribute to depression, and secondly, that depressive states might induce modification of specific gut microbiota species and eventually contribute to more severe depression. The feasibility of both sequences is supported by pre-clinical trials. For instance, research in rodents has shown an onset of depressive behaviour following faecal transplantations from patients with MDD. On the other hand, mental induction of stress and depressive behaviour in rodents resulted in reduced gut microbiota richness and diversity. Synthesis of these chronology dynamics raises important research directions to further understand the role that gut microbiota play in mood-relating behaviours, which holds substantial potential clinical outcomes for persons who experience MDD or related depressive disorders.

Keywords: anxiety; depressive disorder; gut-brain axis; gut microbiota; stress

References

  • Abbott, C.R., Monteiro, M., Small, C.J., Sajedi, A., Smith, K.L., Parkinson, J.R.C., Ghatei, M.A., and Bloom, S.R. (2005). The inhibitory effects of peripheral administration of peptide YY3-36 and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res. 1044, 127–131.CrossrefPubMedGoogle Scholar

  • 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

  • Alper, E. and Ceylan, M.E. (2015). The gut-brain axis: the missing link in depression. Clin. Psychopharmacol. Neurosci. 13, 239–244.CrossrefPubMedGoogle Scholar

  • Aoki-Yoshida, A., Aoki, R., Moriya, N., Goto, T., Kubota, Y., Toyoda, A., Takayama, Y., and Suzuki, C. (2016). Omics studies of the murine intestinal ecosystem exposed to subchronic and mild social defeat stress. J. Proteome. Res. 15, 3126–3138.CrossrefPubMedGoogle Scholar

  • APA. (2013). Diagnostic and Statistical Manual of Mental Disorders-5 (Washington, DC: American Psychiatric Association).Google Scholar

  • Asano, Y., Hiramoto, T., Nishino, R., Aiba, Y., Kimura, T., Yoshihara, K., Koga, Y., and Sudo, N. (2012). Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 303, G1288–G1295.Google Scholar

  • 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.CrossrefPubMedGoogle Scholar

  • 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.PubMedCrossrefGoogle Scholar

  • 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.CrossrefPubMedGoogle Scholar

  • Bakken, J.S., Borody, T., Brandt, L.J., Brill, J.V., Demarco, D.C., Franzos, M.A., Kelly, C., Khoruts, A., Louie, T., Martinelli, L.P., et al. (2011). Treating Clostridium difficile infection with fecal microbiota transplantation. Clin. Gastroenterol. Hepatol. 9, 1044–1049.CrossrefPubMedGoogle Scholar

  • Bangsgaard, B.K.M., Krych, L., Sorensen, D.B., Pang, W., Nielsen, D.S., Josefsen, K., Hansen, L.H., Sorensen, S.J., and Hansen, A.K. (2012). Gut microbiota composition is correlated to grid floor induced stress and behavior in the BALB/c mouse. PLoS One 7, e46231.PubMedCrossrefGoogle Scholar

  • Bercik, P., Park, A.J., Sinclair, D., Khoshdel, A., Lu, J., Huang, X., Deng, Y., Blennerhassett, P.A., Fahnestock, M., Moine, D., et al. (2011). The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol. Motil. 23, 1132–1139.PubMedCrossrefGoogle Scholar

  • Berthoud, H.-R. and Neuhuber, W.L. (2000). Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. 85, 1–17.CrossrefPubMedGoogle Scholar

  • Berthoud, H.-R., Shin, A.C., and Zheng, H. (2011). Obesity surgery and gut-brain communication. Physiol. Behav. 105, 106–119.CrossrefPubMedGoogle Scholar

  • Berton, O., McClung, C.A., DiLeone, R.J., Krishnan, V., Renthal, W., Russo, S.J., Graham, D., Tsankova, N.M., Bolanos, C.A., Rios, M., et al. (2006). Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311, 864–868.CrossrefPubMedGoogle Scholar

  • Bharwani, A., Mian, M.F., Foster, J.A., Surette, M.G., Bienenstock, J., and Forsythe, P. (2016). Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology 63, 217–227.PubMedCrossrefGoogle Scholar

  • Brandt, L.J., Aroniadis, O.C., Mellow, M., Kanatzar, A., Kelly, C., Park, T., Stollman, N., Rohlke, F., and Surawicz, C. (2012). Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am. J. Gastroenterol. 107, 1079–1087.PubMedCrossrefGoogle Scholar

  • Bravo, J.A., Forsytheb, 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.CrossrefGoogle Scholar

  • Carola, V., D’Olimpio, F., Brunamonti, E., Bevilacqua, A., Renzi, P., and Mangia, F. (2004). Anxiety-related behaviour in C57BL/6↔BALB/c chimeric mice. Behav. Brain Res. 150, 25–32.PubMedCrossrefGoogle Scholar

  • Chopra, M.P., Zubritsky, C., Knott, K., Have, T.T., Hadley, T., Coyne, J.C., and Oslin, D.W. (2005). Importance of subsyndromal symptoms of depression in elderly patients. Am. J. Geriatr. Psychiatry 13, 597–606.CrossrefPubMedGoogle Scholar

  • Choudary, P.V., Molnar, M., Evans, S.J., Tomita, H., Li, J.Z., Vawter, M.P., Myers, R.M., Bunney, W.E., Akil, H., Watson, S.J., et al. (2005). Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc. Natl. Acad. Sci. USA 102, 15653–15658.CrossrefGoogle Scholar

  • Clarke, G., Grenham, S., Scully, P., Fitzgerald, P., Moloney, R.D., Shanahan, F., Dinan, T.G., and Cryan, J.F. (2013). The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol. Psychiatry 18, 666–673.CrossrefGoogle Scholar

  • Collins, S.M., Surette, M., and Bercik, P. (2012). The interplay between the intestinal microbiota and the brain. Nat. Rev. Micro. 10, 735–742.CrossrefGoogle Scholar

  • Conn, A.R., Fell, D.I., and Steele, R.D. (1983). Characterization of alpha-keto acid transport across blood-brain barrier in rats. Am. J. Physiol. Endocrinol. Metabol. 245, E253–E260.Google Scholar

  • Conway, T. and Cohen, P.S. (2015). Commensal and pathogenic Escherichia coli metabolism in the gut. Microbiol. Spectr. 3, 1–15.Google Scholar

  • 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.CrossrefPubMedGoogle Scholar

  • Dantzer, R. (2009). Cytokine, sickness behavior, and depression. Immunol. Allergy Clin. North Am. 29, 247–264.PubMedCrossrefGoogle Scholar

  • Date, Y., Murakami, N., Toshinai, K., Matsukura, S., Niijima, A., Matsuo, H., Kangawa, K., and Nakazato, M. (2002). The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 123, 1120–1128.PubMedCrossrefGoogle Scholar

  • Delgardo, P. and Morena, F. (2006). Neurochemistry of mood disorders. The Textbook of Mood Disorders. D.K. Stein, D.J. Kupfer, and A.F. Schatzberg, eds. (Washington, DC: American Psychiatric Publishing), pp. 101–116.Google Scholar

  • Dhaher, R., Damisah, E.C., Wang, H., Gruenbaum, S.E., Ong, C., Zaveri, H.P., Gruenbaum, B.F., and Eid, T. (2014). 5-Aminovaleric acid suppresses the development of severe seizures in the methionine sulfoximine model of mesial temporal lobe epilepsy. Neurobiol. Dis. 67, 18–23.PubMedCrossrefGoogle Scholar

  • Dinan, T.G. and Cryan, J.F. (2013). Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol. Motil. 25, 713–719.CrossrefPubMedGoogle Scholar

  • Dinan, T.G. and Cryan, J.F. (2016). Mood by microbe: towards clinical translation. Genome Med. 8, 36.CrossrefPubMedGoogle Scholar

  • Dinan, T.G., Stilling, R.M., Stanton, C., and Cryan, J.F. (2015). Collective unconscious: how gut microbes shape human behavior. J. Psychiatr. Res. 63, 1–9.PubMedCrossrefGoogle Scholar

  • Drossman, D.A. (1998). Presidential address: gastrointestinal illness and the biopsychosocial model. Psychosom. Med. 60, 258–267.PubMedCrossrefGoogle Scholar

  • Farshim, P., Walton, G., Chakrabarti, B., Givens, I., Saddy, D., Kitchen, I., R Swann, J., and Bailey, A. (2016). Maternal weaning modulates emotional behavior and regulates the gut-brain axis. Sci. Rep. 6, 21958.CrossrefPubMedGoogle Scholar

  • Fendt, M., Schmid, S., Thakker, D.R., Jacobson, L.H., Yamamoto, R., Mitsukawa, K., Maier, R., Natt, F., Husken, D., Kelly, P.H., et al. (2007). mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity. Mol. Psychiatry 13, 970–979.PubMedGoogle Scholar

  • Ferster, C.B. (1973). A functional analysis of depression. Am. Psychol. 28, 857–870.CrossrefGoogle Scholar

  • Foley, J.O. and DuBois, F.S. (1937). Quantitative studies of the vagus nerve in the cat. I. The ratio of sensory to motor fibers. J. Comparat. Neurol. 67, 49–67.CrossrefGoogle Scholar

  • Galley, J.D., Nelson, M., Yu, Z., Dowd, S.E., Walter, J., Kumar, P.S., Lyte, L., and Bailey, M.T. (2014). Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota. BMC Microbiol. 14, 189.PubMedCrossrefGoogle Scholar

  • Gilbert, P. (2005). Evolution and depression: issues and implications. Psychol. Med. 36, 287–297.PubMedCrossrefGoogle Scholar

  • Golden, S.A., Covington, H.E., Berton, O., and Russo, S.J. (2011). A standardized protocol for repeated social defeat stress in mice. Nat. Protoc. 6, 1183–1191.CrossrefPubMedGoogle Scholar

  • Goldney, R.D., Fisher, L.J., Dal Grande, E., and Taylor, A.W. (2004). Subsyndromal depression: prevalence, use of health services and quality of life in an Australian population. Soc. Psychiatry Psychiatr. Epidemiol. 39, 293–298.CrossrefGoogle Scholar

  • Goto, T., Kubota, Y., Tanaka, Y., Iio, W., Moriya, N., and Toyoda, A. (2014). Subchronic and mild social defeat stress accelerates food intake and body weight gain with polydipsia-like features in mice. Behav. Brain Res. 270, 339–348.CrossrefPubMedGoogle Scholar

  • Harkin, A., Kelly, J.P., and Leonard, B.E. (2003). A review of the relevance and validity of olfactory bulbectomy as a model of depression. Clin. Neurosc. Res. 3, 253–262.CrossrefGoogle Scholar

  • Hasin, D.S., Goodwin, R.D., Stinson, F.S., and Grant, B.F. (2005). Epidemiology of major depressive disorder: results from the national epidemiologic survey on alcoholism and related conditions. Arch. Gen. Psychiatry 62, 1097–1106.CrossrefPubMedGoogle Scholar

  • Hassan, A.M., Jain, P., Reichmann, F., Mayerhofer, R., Farzi, A., Schuligoi, R., and Holzer, P. (2014). Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice. Front. Behav. Neurosci. 8, 1–16.Google Scholar

  • Hennessy, M.B., Paik, K.D., Caraway, J.D., Schiml, P.A., and Deak, T. (2011). Proinflammatory activity and the sensitization of depressive-like behavior during maternal separation. Behav. Neurosci. 125, 426–433.CrossrefPubMedGoogle Scholar

  • Hillsley, K. and Grundy, D. (1998). Serotonin and cholecystokinin activate different populations of rat mesenteric vagal afferents. Neurosci. Lett. 255, 63–66.PubMedCrossrefGoogle Scholar

  • Insel, T. (2013). Transforming Diagnosis. National Institute of Mental Health. www.nimh.nih.gov/about/director/2013/transforming-diagnosis.shtml. Accessed 3 January 2017.

  • 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.CrossrefPubMedGoogle Scholar

  • Judd, L.L., Rapaport, M.H., Paulus, M.P., and Brown, J.L. (1994). Subsyndromal symptomatic depression: a new mood disorder? J. Clin. Psychiatry 54, 18–28.Google Scholar

  • Judd, L.L., Paulus, M.P., Wells, K.B., and Rapaport, M.H. (1996). Socioeconomic burden of subsyndromal depressive symptoms and major depression in a sample of the general population. Am. J. Psychiatry 153, 1411–1417.CrossrefGoogle Scholar

  • Judd, L.L., Akiskal, H.S., and Paulus, M.P. (1997). The role and clinical significance of subsyndromal depressive symptoms (SSD) in unipolar major depressive disorder. J. Affect. Disord. 45, 5–18.CrossrefPubMedGoogle Scholar

  • Judd, L.L., Akiskal, H.S., Maser, J.D., Zeller, P.J., Endicott, J., Coryell, W., Paulus, M.P., Kunovac, J.L., Leon, A.C., Mueller, T.I., et al. (1998). A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch. Gen. Psychiatry 55, 694–700.CrossrefPubMedGoogle Scholar

  • Kanter, J.W., Busch, A.M., Weeks, C.E., and Landes, S.J. (2008). The nature of clinical depression: symptoms, syndromes, and behavior analysis. Behav. Anal. 31, 1–21.PubMedCrossrefGoogle Scholar

  • Katon, W., Lin, E.H.B., and Kroenke, K. (2007). The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. Gen. Hosp. Psychiatry 29, 147–155.CrossrefPubMedGoogle Scholar

  • Kelly, J.R., Borre, Y., O’Brien, C., Patterson, E., El Aidy, S., Deane, J., Kennedy, P.J., Beers, S., Scott, K., Moloney, G., et al. (2016). Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J. Psychiatr. Res. 82, 109–118.CrossrefPubMedGoogle Scholar

  • Koda, S., Date, Y., Murakami, N., Shimbara, T., Hanada, T., Toshinai, K., Niijima, A., Furuya, M., Inomata, N., Osuye, K., et al. (2005). The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 146, 2369–2375.CrossrefPubMedGoogle Scholar

  • Koenigs, M. and Grafman, J. (2009). The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav. Brain. Res. 201, 239–243.CrossrefPubMedGoogle Scholar

  • Koves, T.R., Ussher, J.R., Noland, R.C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J.R.B., Newgard, C.B., et al. (2008). Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 7, 45–56.PubMedCrossrefGoogle Scholar

  • Krych, L., Hansen, C.H., Hansen, A.K., van den Berg, F.W., and Nielsen, D.S. (2013). Quantitatively different, yet qualitatively alike: a meta-analysis of the mouse core gut microbiome with a view towards the human gut microbiome. PLoS One 8, e62578.CrossrefPubMedGoogle Scholar

  • Langa, K.M., Valenstein, M.A., Fendrick, A.M., Kabeto, M.U., and Vijan, S. (2004). Extent and cost of informal caregiving for older Americans with symptoms of depression. Am. J. Psychiat. 161, 857–863.CrossrefGoogle Scholar

  • Lyness, J.M., Heo, M., Datto, C.J., Ten Have, T.R., Katz, I.R., Drayer, R., Reynolds, C.F. 3rd, Alexopoulos, G.S., and Bruce, M.L. (2006). Outcomes of minor and subsyndromal depression among elderly patients in primary care settings. Ann. Int. Med. 144, 496–504.CrossrefGoogle Scholar

  • Lyness, J.M., Kim, J., Tu, X., Conwell, Y., King, D.A., and Caine, E.D. (2007). The clinical significance of subsyndromal depression in older primary care patients. Am. J. Geriatr. Psychiatry 15, 214–223.PubMedCrossrefGoogle Scholar

  • Maes, M., Berk, M., Goehler, L., Song, C., Anderson, G., Gałecki, P., and Leonard, B. (2012). Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med. 10, 66.PubMedCrossrefGoogle Scholar

  • Marcinkiewcz, C.A., Mazzone, C.M., D’Agostino, G., Halladay, L.R., Hardaway, J.A., DiBerto, J.F., Navarro, M., Burnham, N., Cristiano, C., Dorrier, C.E., et al. (2016). Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature 537, 97–101.CrossrefPubMedGoogle Scholar

  • Marques-Deak, A., Cizza, G., and Sternberg, E. (2005). Brain-immune interactions and disease susceptibility. Mol. Psychiatry 10, 239–250.PubMedCrossrefGoogle Scholar

  • Mayer, E.A. (2011). Gut feelings: the emerging biology of gut-brain communication. Nat. Rev. Neurosci. 12, 453–466.CrossrefPubMedGoogle Scholar

  • Mittal, R., Debs, L.H., Patel, A.P., Nguyen, D., Patel, K., O’Connor, G., Grati, M.H., Mittal, J., Yan, D., Eshraghi, A.A., et al. (2017). Neurotransmitters: the critical modulators regulating gut-brain axis. J. Cell. Physiol. 232, 2359–2237.CrossrefPubMedGoogle Scholar

  • Miyashita, T. and Williams, C.L. (2006). Epinephrine administration increases neural impulses propagated along the vagus nerve: role of peripheral β-adrenergic receptors. Neurobiol. Learn. Mem. 85, 116–124.PubMedCrossrefGoogle Scholar

  • Morris, G., Berk, M., Carvalho, A., Caso, J.R., Sanz, Y., Walder, K., and Maes, M. (2017). 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. 54, 4432–4451.PubMedCrossrefGoogle Scholar

  • Moussavi, S., Chatterji, S., Verdes, E., Tandon, A., Patel, V., and Ustun, B. (2007). Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370, 851–858.CrossrefPubMedGoogle Scholar

  • Mykletun, A., Bjerkeset, O., Øverland, S., Prince, M., Dewey, M., and Stewart, R. (2009). Levels of anxiety and depression as predictors of mortality: the HUNT study. Br. J. Psychiatry 195, 118–125.CrossrefGoogle Scholar

  • Nankova, B.B., Agarwal, R., MacFabe, D.F., and La Gamma, E.F. (2014). Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells – possible relevance to autism spectrum disorders. PLoS One 9, e103740.PubMedCrossrefGoogle Scholar

  • Naseribafrouei, A., Hestad, K., Avershina, E., Sekelja, M., Linlokken, A., Wilson, R., and Rudi, K. (2014). Correlation between the human fecal microbiota and depression. Neurogastroenterol. Motil. 26, 1155–1162.CrossrefPubMedGoogle Scholar

  • Neufeld, K.M., Kang, N., Bienenstock, J., and Foster, J.A. (2011). Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol. Motil. 23, 255–264, e119.Google Scholar

  • 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.CrossrefPubMedGoogle Scholar

  • O’Mahony, S.M., Clarke, G., Borre, Y.E., Dinan, T.G., and Cryan, J.F. (2015). Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav. Brain Res. 277, 32–48.PubMedCrossrefGoogle Scholar

  • Østergaard, S.D., Jensen, S.O.W., and Bech, P. (2011). The heterogeneity of the depressive syndrome: when numbers get serious. Acta Psychiatr. Scand. 124, 495–496.PubMedCrossrefGoogle Scholar

  • Otmishi, P., Gordon, J., El-Oshar, S., Li, H., Guardiola, J., Saad, M., Proctor, M., and Yu, J. (2008). Neuroimmune interaction in inflammatory diseases. Clin. Med. Circ. Resp. Pulm. Med. 2, 35–44.Google Scholar

  • Painsipp, E., Herzog, H., Sperk, G., and Holzer, P. (2011). Sex-dependent control of murine emotional-affective behaviour in health and colitis by peptide YY and neuropeptide Y. Br. J. Pharmacol. 163, 1302–1314.PubMedCrossrefGoogle Scholar

  • Park, A.J., Collins, J., Blennerhassett, P.A., Ghia, J.E., Verdu, E.F., Bercik, P., and Collins, S.M. (2013). Altered colonic function and microbiota profile in a mouse model of chronic depression. Neurogastroenterol. Motil. 25, 733–e575.Google Scholar

  • Parker, G. (2005). Beyond major depression. Psychol. Med. 41, 467–474.Google Scholar

  • Parker, G., Roy, K., Mitchell, P., Wilhelm, K., Malhi, G., and Hadzi-Pavlovic, D. (2002). Atypical depression: a reappraisal. Am. J. Psychiatry 159, 1470–1479.CrossrefPubMedGoogle Scholar

  • Peters, J.H., Ritter, R.C., and Simasko, S.M. (2006). Leptin and CCK selectively activate vagal afferent neurons innervating the stomach and duodenum. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1544–R1549.Google Scholar

  • Raedler, T.J. (2011). Inflammatory mechanisms in major depressive disorder. Curr. Opin. Psychiatry 24, 519–525.CrossrefPubMedGoogle Scholar

  • Raison, C.L. and Miller, A.H. (2011). Is depression an inflammatory disorder? Curr. Psychiatry Rep. 13, 467–475.CrossrefPubMedGoogle Scholar

  • Reimold, M., Batra, A., Knobel, A., Smolka, M.N., Zimmer, A., Mann, K., Solbach, C., Reischl, G., Schwarzler, F., Grunder, G., et al. (2008). Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: a [11C]DASB PET study. Mol. Psychiatry 13, 606–613.CrossrefPubMedGoogle Scholar

  • Ross, D.A., Travis, M.J., and Arbuckle, M.R. (2015). The future of psychiatry as clinical neuroscience: why not now? J. Am. Med. Assoc. Psychiatry 72, 413–414.Google Scholar

  • Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A.A., Stewart, J.W., Warden, D., Niederehe, G., Thase, M.E., Lavori, P.W., Lebowitz, B.D., et al. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry 163, 1905–1917.CrossrefPubMedGoogle Scholar

  • Sharpley, C.F. and Bitsika, V. (2014). Validity, reliability and prevalence of four ‘clinical content’ subtypes of depression. Behav. Brain Res. 259, 9–15.CrossrefPubMedGoogle Scholar

  • Shilov, V., Lizko, N., Borisova, O., and Prokhorov, V. (1971). Changes in the microflora of man during long-term confinement. Life Sci. Space Res. 9, 43–49.PubMedGoogle Scholar

  • Smirnov, K.V. and Lizko, N.N. (1987). Problems of space gastroenterology and microenvironment. Nahrung 31, 563–566.CrossrefPubMedGoogle Scholar

  • Song, C. and Leonard, B.E. (2005). The olfactory bulbectomised rat as a model of depression. Neurosci. Biobehav. Rev. 29, 627–647.CrossrefPubMedGoogle Scholar

  • 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.PubMedCrossrefGoogle Scholar

  • Tremaroli, V. and Backhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature 489, 242–249.PubMedCrossrefGoogle Scholar

  • Uneyama, H., Niijima, A., San Gabriel, A., and Torii, K. (2006). Luminal amino acid sensing in the rat gastric mucosa. Am. J. Physiol. Gastrointest. Liver Physiol. 291, G1163–G1170.Google Scholar

  • Vanitallie, T. (2005). Subsyndromal depression in the elderly: underdiagnosed and undertreated. Metabolism 54, 39–44.CrossrefPubMedGoogle Scholar

  • Walker, E., McGee, R.E., and Druss, B.G. (2015). Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. J. Am. Med. Assoc. Psychiatry 72, 334–341.Google Scholar

  • Willner, P. (1983). Dopamine and depression: a review of recent evidence. I. Empirical studies. Brain Res. Rev. 6, 211–224.Google Scholar

  • Youngster, I., Sauk, J., Pindar, C., Wilson, R.G., Kaplan, J.L., Smith, M.B., Alm, E.J., Gevers, D., Russell, G.H., and Hohmann, E.L. (2014). Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin. Infect. Dis. 58, 1515–1522.PubMedCrossrefGoogle Scholar

  • Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., Zeng, L., Chen, J., Fan, S., Du, X., et al. (2016). Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol. Psychiatry 21, 786–796.CrossrefPubMedGoogle Scholar

About the article

Received: 2017-08-22

Accepted: 2017-12-08

Published Online: 2018-02-05


Citation Information: Reviews in the Neurosciences, 20170072, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2017-0072.

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