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

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, 127–131.10.1016/j.brainres.2005.03.011Search in Google Scholar PubMed

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, 254–257.10.1016/j.jad.2016.05.038Search in Google Scholar PubMed

Alper, E. and Ceylan, M.E. (2015). The gut-brain axis: the missing link in depression. Clin. Psychopharmacol. Neurosci. 13, 239–244.10.9758/cpn.2015.13.3.239Search in Google Scholar PubMed

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, 3126–3138.10.1021/acs.jproteome.6b00262Search in Google Scholar PubMed

APA. (2013). Diagnostic and Statistical Manual of Mental Disorders-5 (Washington, DC: American Psychiatric Association).Search in 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–G1295.10.1152/ajpgi.00341.2012Search in 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, 146–155.10.1002/(SICI)1098-2302(199909)35:2<146::AID-DEV7>3.0.CO;2-GSearch in Google Scholar PubMed

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, 1509–1519.10.1128/IAI.00862-09Search in Google Scholar PubMed

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, 397–407.10.1016/j.bbi.2010.10.023Search in Google Scholar PubMed

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, 1044–1049.10.1016/j.cgh.2011.08.014Search in Google Scholar PubMed

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, e46231.10.1371/journal.pone.0046231Search in Google Scholar PubMed

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, 1132–1139.10.1111/j.1365-2982.2011.01796.xSearch in Google Scholar PubMed

Berthoud, H.-R. and Neuhuber, W.L. (2000). Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. 85, 1–17.10.1016/S1566-0702(00)00215-0Search in Google Scholar PubMed

Berthoud, H.-R., Shin, A.C., and Zheng, H. (2011). Obesity surgery and gut-brain communication. Physiol. Behav. 105, 106–119.10.1016/j.physbeh.2011.01.023Search in Google Scholar PubMed

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, 864–868.10.1126/science.1120972Search in Google Scholar PubMed

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, 217–227.10.1016/j.psyneuen.2015.10.001Search in Google Scholar PubMed

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, 1079–1087.10.1038/ajg.2012.60Search in Google Scholar PubMed

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, 16050–16055.10.1073/pnas.1102999108Search in Google 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, 25–32.10.1016/S0166-4328(03)00217-1Search in Google Scholar PubMed

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, 597–606.10.1097/00019442-200507000-00008Search in Google Scholar PubMed

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, 15653–15658.10.1073/pnas.0507901102Search in Google Scholar PubMed PubMed Central

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, 666–673.10.1038/mp.2012.77Search in Google Scholar PubMed

Collins, S.M., Surette, M., and Bercik, P. (2012). The interplay between the intestinal microbiota and the brain. Nat. Rev. Micro. 10, 735–742.10.1038/nrmicro2876Search in Google Scholar PubMed

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–E260.10.1152/ajpendo.1983.245.3.E253Search in Google Scholar PubMed

Conway, T. and Cohen, P.S. (2015). Commensal and pathogenic Escherichia coli metabolism in the gut. Microbiol. Spectr. 3, 1–15.10.1128/9781555818883.ch16Search in 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, 701.10.1038/nrn3346Search in Google Scholar PubMed

Dantzer, R. (2009). Cytokine, sickness behavior, and depression. Immunol. Allergy Clin. North Am. 29, 247–264.10.1016/j.iac.2009.02.002Search in Google Scholar PubMed PubMed Central

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, 1120–1128.10.1053/gast.2002.35954Search in Google Scholar PubMed

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.Search in 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, 18–23.10.1016/j.nbd.2014.03.006Search in Google Scholar PubMed PubMed Central

Dinan, T.G. and Cryan, J.F. (2013). Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol. Motil. 25, 713–719.10.1111/nmo.12198Search in Google Scholar PubMed

Dinan, T.G. and Cryan, J.F. (2016). Mood by microbe: towards clinical translation. Genome Med. 8, 36.10.1186/s13073-016-0292-1Search in Google Scholar PubMed PubMed Central

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, 1–9.10.1016/j.jpsychires.2015.02.021Search in Google Scholar PubMed

Drossman, D.A. (1998). Presidential address: gastrointestinal illness and the biopsychosocial model. Psychosom. Med. 60, 258–267.10.1097/00006842-199805000-00007Search in Google Scholar PubMed

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, 21958.10.1038/srep21958Search in Google Scholar PubMed PubMed Central

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, 970–979.10.1038/sj.mp.4002073Search in Google Scholar PubMed

Ferster, C.B. (1973). A functional analysis of depression. Am. Psychol. 28, 857–870.10.1037/h0035605Search in Google Scholar PubMed

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, 49–67.10.1002/cne.900670104Search in Google 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, 189.10.1186/1471-2180-14-189Search in Google Scholar PubMed PubMed Central

Gilbert, P. (2005). Evolution and depression: issues and implications. Psychol. Med. 36, 287–297.10.1017/S0033291705006112Search in Google Scholar PubMed

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, 1183–1191.10.1038/nprot.2011.361Search in Google Scholar PubMed PubMed Central

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, 293–298.10.1007/s00127-004-0745-5Search in Google Scholar PubMed

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, 339–348.10.1016/j.bbr.2014.05.040Search in Google Scholar PubMed

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, 253–262.10.1016/S1566-2772(03)00087-2Search in Google 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, 1097–1106.10.1001/archpsyc.62.10.1097Search in Google Scholar PubMed

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, 1–16.10.3389/fnbeh.2014.00386Search in 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, 426–433.10.1037/a0023559Search in Google Scholar PubMed

Hillsley, K. and Grundy, D. (1998). Serotonin and cholecystokinin activate different populations of rat mesenteric vagal afferents. Neurosci. Lett. 255, 63–66.10.1016/S0304-3940(98)00690-9Search in Google Scholar PubMed

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

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, 186–194.10.1016/j.bbi.2015.03.016Search in Google Scholar PubMed

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, 18–28.10.2165/00023210-199401060-00001Search in 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, 1411–1417.10.1176/ajp.153.11.1411Search in Google 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, 5–18.10.1016/S0165-0327(97)00055-4Search in Google Scholar PubMed

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, 694–700.10.1001/archpsyc.55.8.694Search in Google Scholar PubMed

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, 1–21.10.1007/BF03392158Search in Google Scholar PubMed PubMed Central

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, 147–155.10.1016/j.genhosppsych.2006.11.005Search in Google Scholar PubMed

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, 109–118.10.1016/j.jpsychires.2016.07.019Search in Google Scholar PubMed

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, 2369–2375.10.1210/en.2004-1266Search in Google Scholar PubMed

Koenigs, M. and Grafman, J. (2009). The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav. Brain. Res. 201, 239–243.10.1016/j.bbr.2009.03.004Search in Google Scholar PubMed PubMed Central

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, 45–56.10.1016/j.cmet.2007.10.013Search in Google Scholar PubMed

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, e62578.10.1371/journal.pone.0062578Search in Google Scholar PubMed PubMed Central

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, 857–863.10.1176/appi.ajp.161.5.857Search in Google Scholar PubMed

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, 496–504.10.7326/0003-4819-144-7-200604040-00008Search in Google Scholar PubMed

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, 214–223.10.1097/01.JGP.0000235763.50230.83Search in Google Scholar PubMed

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, 66.10.1186/1741-7015-10-66Search in Google Scholar PubMed

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, 97–101.10.1038/nature19318Search in Google Scholar PubMed

Marques-Deak, A., Cizza, G., and Sternberg, E. (2005). Brain-immune interactions and disease susceptibility. Mol. Psychiatry 10, 239–250.10.1038/sj.mp.4001643Search in Google Scholar PubMed

Mayer, E.A. (2011). Gut feelings: the emerging biology of gut-brain communication. Nat. Rev. Neurosci. 12, 453–466.10.1038/nrn3071Search in Google Scholar PubMed

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, 2359–2237.10.1002/jcp.25518Search in Google Scholar PubMed

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, 116–124.10.1016/j.nlm.2005.08.013Search in Google Scholar PubMed

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, 4432–4451.10.1007/s12035-016-0004-2Search in Google Scholar PubMed

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, 851–858.10.1016/S0140-6736(07)61415-9Search in Google Scholar PubMed

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, 118–125.10.1192/bjp.bp.108.054866Search in Google Scholar PubMed

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, e103740.10.1371/journal.pone.0103740Search in Google Scholar PubMed PubMed Central

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, 1155–1162.10.1111/nmo.12378Search in Google Scholar PubMed

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, e119.10.1111/j.1365-2982.2010.01620.xSearch in Google Scholar PubMed

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, 263–267.10.1016/j.biopsych.2008.06.026Search in Google Scholar PubMed

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, 32–48.10.1016/j.bbr.2014.07.027Search in Google Scholar PubMed

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, 495–496.10.1111/j.1600-0447.2011.01744.xSearch in Google Scholar PubMed

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, 35–44.10.4137/CCRPM.S547Search in 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, 1302–1314.10.1111/j.1476-5381.2011.01326.xSearch in Google Scholar PubMed PubMed Central

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–e575.10.1111/nmo.12153Search in Google Scholar PubMed PubMed Central

Parker, G. (2005). Beyond major depression. Psychol. Med. 41, 467–474.10.1017/S0033291704004210Search in 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, 1470–1479.10.1176/appi.ajp.159.9.1470Search in Google Scholar PubMed

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–R1549.10.1152/ajpregu.00811.2005Search in Google Scholar PubMed

Raedler, T.J. (2011). Inflammatory mechanisms in major depressive disorder. Curr. Opin. Psychiatry 24, 519–525.10.1097/YCO.0b013e32834b9db6Search in Google Scholar PubMed

Raison, C.L. and Miller, A.H. (2011). Is depression an inflammatory disorder? Curr. Psychiatry Rep. 13, 467–475.10.1007/s11920-011-0232-0Search in Google Scholar PubMed PubMed Central

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, 606–613.10.1038/sj.mp.4002149Search in Google Scholar PubMed

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, 413–414.10.1001/jamapsychiatry.2014.3199Search in Google Scholar PubMed PubMed Central

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, 1905–1917.10.1176/ajp.2006.163.11.1905Search in Google Scholar PubMed

Sharpley, C.F. and Bitsika, V. (2014). Validity, reliability and prevalence of four ‘clinical content’ subtypes of depression. Behav. Brain Res. 259, 9–15.10.1016/j.bbr.2013.10.032Search in Google Scholar PubMed

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.Search in Google Scholar PubMed

Smirnov, K.V. and Lizko, N.N. (1987). Problems of space gastroenterology and microenvironment. Nahrung 31, 563–566.10.1002/food.19870310572Search in Google Scholar PubMed

Song, C. and Leonard, B.E. (2005). The olfactory bulbectomised rat as a model of depression. Neurosci. Biobehav. Rev. 29, 627–647.10.1016/j.neubiorev.2005.03.010Search in Google Scholar PubMed

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, 263–275.10.1113/jphysiol.2004.063388Search in Google Scholar PubMed

Tremaroli, V. and Backhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature 489, 242–249.10.1038/nature11552Search in Google Scholar PubMed

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–G1170.10.1152/ajpgi.00587.2005Search in Google Scholar

Vanitallie, T. (2005). Subsyndromal depression in the elderly: underdiagnosed and undertreated. Metabolism 54, 39–44.10.1016/j.metabol.2005.01.012Search in Google Scholar PubMed

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, 334–341.10.1001/jamapsychiatry.2014.2502Search in Google Scholar

Willner, P. (1983). Dopamine and depression: a review of recent evidence. I. Empirical studies. Brain Res. Rev. 6, 211–224.10.1016/0165-0173(83)90005-XSearch in 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, 1515–1522.10.1093/cid/ciu135Search in Google Scholar PubMed PubMed Central

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, 786–796.10.1038/mp.2016.44Search in Google Scholar PubMed