Chapter 22 : Probiotics in Neurology and Psychiatry

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Probiotics are live nonpathogenic organisms that promote beneficial health effects when ingested. Increasing numbers of reports indicate that probiotics may have therapeutic potential in disorders ranging from atopic dermatitis to arthritis, highlighting the systemic impact of these organisms. While probiotics have been proposed as adjuvant therapy for depression, to date little is known of the ability of probiotic treatment to modulate brain function. The brain and the gut are engaged in constant bidirectional communication. Such communication becomes apparent when alterations in gastrointestinal (GI) function are communicated to the brain, bringing about the perception of visceral events such as nausea, satiety, and pain or when, in turn, stressful experiences lead to altered GI secretions and motility. This communication system involves neural pathways as well as immune and endocrine mechanisms. Consistent observations have suggested that patients with major depression who are otherwise healthy have activated inflammatory pathways, as indicated by increased proinflammatory cytokines, increased acute-phase proteins, and greater expression of chemokines and adhesion molecules. In addition to direct neural pathways, the gut also communicates to the brain utilizing hormonal signaling pathways that involve the release of gut peptides from enteroendocrine cells which can act directly on the brain at the area postrema, one of the circumventricular organs that lie outside the blood-brain barrier. Future research should be aimed at determining specific mechanisms involved in linking the human microbiota in general with central nervous system (CNS) homeostasis and function.

Citation: Forsythe P, Bienestock J. 2008. Probiotics in Neurology and Psychiatry, p 285-298. In Versalovic J, Wilson M (ed), Therapeutic Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555815462.ch22

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Tumor Necrosis Factor
Lactic Acid Bacteria
Omega-3 Fatty Acids
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Figure 1

The brain-gut-microbiota axis. Gut microbiota organisms are in intimate contact with the immune and nervous systems of the host. Microorganisms alter the metabolic profiles and nutrient content of the gut, which may influence neuroendocrine responses. Commensal organisms, pathogens, and probiotics have the potential to influence major communication routes between the gut and brain. See the text for details.

Citation: Forsythe P, Bienestock J. 2008. Probiotics in Neurology and Psychiatry, p 285-298. In Versalovic J, Wilson M (ed), Therapeutic Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555815462.ch22
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1. Alesci, S.,, P. E. Martinez,, S. Kelkar,, I. Ilias,, D. S. Ronsaville,, S. J. Listwak,, A. R. Ayala,, J. Licinio,, H. K. Gold,, M. A. Kling,, G. P. Chrousos, and, P. W. Gold. 2005. Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications. J. Clin. Endocrinol. Metab. 90:25222530.
2. Alm, J. S.,, J. Swartz,, G. Lilja,, A. Scheynius,, and G. Pershagen. 1999. Atopy in children of families with an anthroposophic lifestyle. Lancet 353:14851488.
3. Arborelius, L.,, M. J. Owens,, P. M. Plotsky, and, C. B. Nemeroff. 1999. The role of corticotropin-releasing factor in depression and anxiety disorders. J. Endocrinol. 160:112.
4. Aston-Jones, G.,, M. Ennis,, V. A. Pieribone,, W. T. Nickell, and, M. T. Shipley. 1986. The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science 234:734737.
5. Aston-Jones, G.,, J. Rajkowski,, P. Kubiak,, R. J. Valentino, and, M. T. Shipley. 1996. Role of the locus coeruleus in emotional activation. Prog. Brain Res. 107:379402.
6. Backhed, F.,, H. Ding,, T. Wang,, L. V. Hooper,, G. Y. Koh,, A. Nagy,, C. F. Semenkovich, and, J. I. Gordon. 2004. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 101:1571815723.
7. Backhed, F.,, R. E. Ley,, J. L. Sonnenburg,, D. A. Peterson, and, J. I. Gordon. 2005. Host-bacterial mutualism in the human intestine. Science 307:19151920.
8. Baharav, E.,, F. Mor,, M. Halpern, and, A. Weinberger. 2004. Lactobacillus GG bacteria ameliorate arthritis in Lewis rats. J. Nutr. 134:19641969.
9. Bailey, M. T., and, C. L. Coe. 1999. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev. Psychobiol. 35:146155.
10. Bailey, M. T.,, G. R. Lubach, and, C. L. Coe. 2004. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J. Pediatr. Gastroenterol. Nutr. 38:414421.
11. Bell, I. R.,, M. L. Jasnoski,, J. Kagan, and, D. S. King. 1991. Depression and allergies: survey of a nonclinical population. Psychother. Psychosom. 55:2431.
12. Benton, D.,, C. Williams, and, A. Brown. 2007. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61:355361.
13. Berglund, M. M.,, P. A. Hipskind, and, D. R. Gehlert. 2003. Recent developments in our understanding of the physiological role of PP-fold peptide receptor subtypes. Exp. Biol. Med. (Maywood) 228:217244.
14. Bjorksten, B.,, P. Naaber,, E. Sepp, and, M. Mikelsaar. 1999. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin. Exp. Allergy 29:342346.
15. Bjorksten, B.,, E. Sepp,, K. Julge,, T. Voor, and, M. Mikelsaar. 2001. Allergy development and the intestinal microflora during the first year of life. J. Allergy Clin. Immunol. 108:516520.
16. Bjornebekk, A.,, A. A. Mathe, and, S. Brene. 2006. Running has differential effects on NPY, opiates, and cell proliferation in an animal model of depression and controls. Neuropsychopharmacology 31:256264.
17. Bolte, E. R. 1998. Autism and Clostridium tetani. Med. Hypotheses 51:133144.
18. Bomba, A.,, R. Nemcova,, S. Gancarcikova,, R. Herich,, P. Guba,, and D. Mudronova. 2002. Improvement of the probiotic effect of microorganisms by their combination with maltodextrins, fructo-oligosaccharides and polyunsaturated fatty acids. Br. J. Nutr. 88(Suppl. 1):S95–S99.
19. Borgland, S. L.,, S. A. Taha,, F. Sarti,, H. L. Fields,, and A. Bonci. 2006. Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 49:589601.
20. Borrielo,, S. P. 2002. The normal flora of the gastrointestinal tract, p. 124. In A. L. Hart,, A.J. Stagg,, H. Graffner,, H. Glise,, P. Falk,, and N. A. Kamm (ed.), Gut Ecology. Cromwell Press, Trowbridge, United Kingdom.
21. Bottiglieri, T.,, M. Laundy,, R. Crellin,, B. K. Toone,, M. W. Carney, and, E. H. Reynolds. 2000. Homocysteine, folate, methylation, and monoamine metabolism in depression. J. Neurol. Neurosurg. Psychiatry 69:228232.
22. Boutrel, B.,, P. J. Kenny,, S. E. Specio,, R. Martin-Fardon,, A. Markou,, G. F. Koob,, and L. de Lecea. 2005. Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc. Natl. Acad. Sci. USA 102:1916819173.
23. Braat, H., J. van den Brande,, E. van Tol,, D. Hommes,, M. Peppelenbosch,, and S. van Deventer. 2004. Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4 T cells via modulation of dendritic cell function. Am. J. Clin. Nutr. 80:16181625.
24. Browning, K. N., and, D. Mendelowitz. 2003. Musings on the wanderer: what’s new in our understanding of vago-vagal reflexes? II. Integration of afferent signaling from the viscera by the nodose ganglia. Am. J. Physiol. Gastrointest. Liver Physiol. 284:G8–G14.
25. Cameron, J., and, E. Doucet. 2007. Getting to the bottom of feeding behaviour: who’s on top? Appl. Physiol. Nutr. Metab. 32:177189.
26. Capuron, L., and, R. Dantzer. 2003. Cytokines and depression: the need for a new paradigm. Brain Behav. Immun. 17(Suppl 1):S119–S124.
27. Carlini, V. P.,, M. M. Varas,, A. B. Cragnolini,, H. B. Schioth,, T. N. Scimonelli, and, S. R. de Barioglio. 2004. Differential role of the hippocampus, amygdala, and dorsal raphe nucleus in regulating feeding, memory, and anxiety-like behavioral responses to ghrelin. Biochem. Biophys. Res. Commun. 313:635641.
28. Cebra, J. J. 1999. Influences of microbiota on intestinal immune system development. Am. J. Clin. Nutr. 69:1046S–1051S.
29. Centanni, S., F. Di Marco,, F. Castagna,, B. Boveri,, F. Casanova,, and A. Piazzini. 2000. Psychological issues in the treatment of asthmatic patients. Respir. Med. 94:742749.
30. Chang, H. Y.,, H. Mashimo, and, R. K. Goyal. 2003. Musings on the wanderer: what’s new in our understanding of vagovagal reflex? IV. Current concepts of vagal efferent projections to the gut. Am. J. Physiol. Gastrointest. Liver Physiol. 284:G357–G366.
31. Chen, B.,, D. Dowlatshahi,, G. M. MacQueen,, J. F. Wang, and, L. T. Young. 2001. Increased hippocampal BDNF immuno-reactivity in subjects treated with antidepressant medication. Biol. Psychiatry 50:260265.
32. Christensen, H. R.,, H. Frokiaer, and, J. J. Pestka. 2002. Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J. Immunol. 168:171178.
33. Clarke, M. B.,, D. T. Hughes,, C. Zhu,, E. C. Boedeker,, and V. Sperandio. 2006. The QseC sensor kinase: a bacterial adrenergic receptor. Proc. Natl. Acad. Sci. USA. 103:1042010425.
34. Coburn, S. P.,, J. D. Mahuren,, B. S. Wostmann,, D. L. Snyder, and, D. W. Townsend. 1989. Role of intestinal microflora in the metabolism of vitamin B-6 and 4’ -deoxypyridoxine examined using germfree guinea pigs and rats. J. Nutr. 119:181188.
35. Crucian, G. P.,, J. D. Hughes,, A. M. Barrett,, D. J. Williamson,, R. M. Bauer,, D. Bowers, and, K. M. Heilman. 2000. Emotional and physiological responses to false feedback. Cortex 36:623647.
36. Drossman, D. A. 1998. Presidential address: gastrointestinal illness and the biopsychosocial model. Psychosom. Med. 60:258267.
37. Dunn, A. J.,, J. Wang, and, T. Ando. 1999. Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv. Exp. Med. Biol. 461:117127.
38. Dwivedi, Y.,, H. S. Rizavi,, R. R. Conley,, R. C. Roberts,, C. A. Tamminga, and, G. N. Pandey. 2003. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch. Gen. Psychiatry 60:804815.
39. Elmer, G. W., and, R. P. Remmel. 1984. Role of the intestinal microflora in clonazepam metabolism in the rat. Xenobiotica 14:829840.
40. Finegold, S. M.,, D. Molitoris,, Y. Song,, C. Liu,, M. L. Vaisanen,, E. Bolte,, M. McTeague,, R. Sandler,, H. Wexler,, E. M. Marlowe,, M. D. Collins,, P. A. Lawson,, P. Summanen,, M. Baysallar,, T. J. Tomzynski,, E. Read,, E. Johnson,, R. Rolfe,, P. Nasir,, H. Shah,, D. A. Haake,, P. Manning,, and A. Kaul. 2002. Gastrointestinal microflora studies in late-onset autism. Clin. Infect. Dis. 35(Suppl. 1):S6–S16.
41. Freeman, M. P.,, J. R. Hibbeln,, K. L. Wisner,, J. M. Davis,, D. Mischoulon,, M. Peet,, P. E. Keck Jr.,, L. B. Marangell,, A. J. Richardson,, J. Lake, and, A. L. Stoll. 2006. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J. Clin. Psychiatry 67:19541967.
42. Frommberger, U. H.,, J. Bauer,, P. Haselbauer,, A. Fraulin,, D. Riemann,, and M. Berger. 1997. Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur. Arch. Psychiatry Clin. Neurosci. 247:228233.
43. Gao, H. M.,, J. Jiang,, B. Wilson,, W. Zhang,, J. S. Hong,, and B. Liu. 2002. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J. Neurochem. 81:12851297.
44. George, S. E.,, R. W. Chadwick,, M. J. Kohan,, J. C. Allison,, R. W. Williams,, and J. Chang. 1994. Role of the intestinal microbiota in the activation of the promutagen 2,6-dinitrotoluene to mutagenic urine metabolites and comparison of GI enzyme activities in germ-free and conventionalized male Fischer 344 rats. Cancer Lett. 79:181187.
45. Ghosh, S., D. van Heel, and, R. J. Playford. 2004. Probiotics in inflammatory bowel disease: is it all gut flora modulation? Gut 53:620622.
46. Gill, S. R.,, M. Pop,, R. T. Deboy,, P. B. Eckburg,, P. J. Turnbaugh,, B. S. Samuel,, J. I. Gordon,, D. A. Relman,, C. M. Fraser-Liggett, and, K. E. Nelson. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312:13551359.
47. Gionchetti, P.,, F. Rizzello,, U. Helwig,, A. Venturi,, K. M. Lammers,, P. Brigidi,, B. Vitali,, G. Poggioli,, M. Miglioli,, and M. Campieri. 2003. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 124:12021209.
48. Giordano, R.,, A. Picu,, F. Broglio,, L. Bonelli,, M. Baldi,, R. Berardelli,, E. Ghigo,, and E. Arvat. 2004. Ghrelin, hypothalamus-pituitary-adrenal (HPA) axis and Cushing’s syndrome. Pituitary 7:243248.
49. Giordano, R.,, M. Pellegrino,, A. Picu,, L. Bonelli,, M. Balbo,, R. Berardelli,, F. Lanfranco,, E. Ghigo,, and E. Arvat. 2006. Neuroregulation of the hypothalamus-pituitary-adrenal (HPA) axis in humans: effects of GABA-, mineralocorticoid-, and GH-Secretagogue-receptor modulation. ScientificWorld-Journal 6:111.
50. Goehler, L. E.,, R. P. Gaykema,, N. Opitz,, R. Reddaway,, N. Badr,, and M. Lyte. 2005. Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav. Immun. 19:334344.
51. Goethe, J. W.,, R. Maljanian,, S. Wolf,, P. Hernandez,, and Y. Cabrera. 2001. The impact of depressive symptoms on the functional status of inner-city patients with asthma. Ann. Allergy Asthma Immunol. 87:205210.
52. Gruenwald, J.,, H. J. Graubaum, and, A. Harde. 2002. Effect of a probiotic multivitamin compound on stress and exhaustion. Adv. Ther. 19:141150.
53. Harris, G. C.,, M. Wimmer, and, G. Aston-Jones. 2005. A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437:556559.
54. Hart, A. L.,, K. Lammers,, P. Brigidi,, B. Vitali,, F. Rizzello,, P. Gionchetti,, M. Campieri,, M. A. Kamm,, S. C. Knight, and, A. J. Stagg. 2004. Modulation of human dendritic cell pheno-type and function by probiotic bacteria. Gut 53:16021609.
55. Hestad, K. A.,, S. Tonseth,, C. D. Stoen,, T. Ueland,, and P. Auk-rust. 2003. Raised plasma levels of tumor necrosis factor alpha in patients with depression: normalization during electroconvulsive therapy. J. ECT 19:183188.
56. Hirano, S.,, S. Miyata, and, J. Kamei. 2007. Antidepressant-like effect of leptin in streptozotocin-induced diabetic mice. Pharmacol. Biochem. Behav. 86:2731.
57. Holdeman, L. V.,, I. J. Good, and, W. E. Moore. 1976. Human fecal flora: variation in bacterial composition within individuals and a possible effect of emotional stress. Appl. Environ. Microbiol. 31:359375.
58. Holsboer, F. 2003. The role of peptides in treatment of psychiatric disorders. J. Neural Transm. Suppl. 2003:1734.
59. Hooper, L. V.,, M. H. Wong,, A. Thelin,, L. Hansson,, P. G. Falk, and, J. I. Gordon. 2001. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291:881884.
60. Horrobin, D. F. 2002. Food, micronutrients, and psychiatry. Int. Psychogeriatr. 14:331334.
61. Hou, C.,, F. Jia,, Y. Liu, and, L. Li. 2006. CSF serotonin, 5-hydroxyindolacetic acid and neuropeptide Y levels in severe major depressive disorder. Brain Res. 1095:154158.
62. Ishida, H.,, Y. Shirayama,, M. Iwata, and, R. Kawahara. 2005. Subchronic treatment with imipramine ameliorates the decreased number in neuropeptide Y-positive cells in the hippocampus of learned helplessness rats. Brain Res. 1046:239243.
63. Ishida, H.,, Y. Shirayama,, M. Iwata,, S. Katayama,, A. Yamamoto,, R. Kawahara,, and K. Nakagome. 2007. Infusion of neuropeptide Y into CA3 region of hippocampus produces antidepressant-like effect via Y1 receptor. Hippocampus 17:271280.
64. Iyer, L. M.,, L. Aravind,, S. L. Coon,, D. C. Klein, and, E. V. Koonin. 2004. Evolution of cell-cell signaling in animals: did late horizontal gene transfer from bacteria have a role? Trends Genet. 20:292299.
65. Jaszberenyi, M.,, E. Bujdoso,, Z. Bagosi, and, G. Telegdy. 2006. Mediation of the behavioral, endocrine and thermoregula-tory actions of ghrelin. Horm. Behav. 50:266273.
66. Kahl, K. G.,, S. Rudolf,, B. M. Stoeckelhuber,, L. Dibbelt,, H. B. Gehl,, K. Markhof,, F. Hohagen,, and U. Schweiger. 2005. Bone mineral density, markers of bone turnover, and cytokines in young women with borderline personality disorder with and without comorbid major depressive disorder. Am. J. Psychiatry 162:168174.
67. Kalliomaki, M.,, S. Salminen,, H. Arvilommi,, P. Kero,, P. Koskinen,, and E. Isolauri. 2001. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 357:10761079.
68. Kalliomaki, M.,, S. Salminen,, T. Poussa,, H. Arvilommi, and, E. Isolauri. 2003. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 361:18691871.
69. Kamiya, T.,, L. Wang,, P. Forsythe,, G. Goettsche,, Y. Mao,, Y. Wang,, G. Tougas,, and J. Bienenstock. 2006. Inhibitory effects of Lactobacillus reuteri on visceral pain induced by colorectal distension in Sprague-Dawley rats. Gut 55:191196.
70. Kankaanpaa, P. E.,, B. Yang,, H. P. Kallio,, E. Isolauri, and, S. J. Salminen. 2002. Influence of probiotic supplemented infant formula on composition of plasma lipids in atopic infants. J. Nutr. Biochem. 13:364369.
71. Karege, F.,, G. Perret,, G. Bondolfi,, M. Schwald,, G. Bertschy, and, J. M. Aubry. 2002. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 109:143148.
72. Karege, F.,, G. Vaudan,, M. Schwald,, N. Perroud, and, R. La Harpe. 2005. Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res. Mol. Brain Res. 136:2937.
73. Kendler, K. S.,, L. M. Thornton, and, C. O. Gardner. 2000. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis. Am. J. Psychiatry 157:12431251.
74. Kipnis, J.,, E. Yoles,, H. Schori,, E. Hauben,, I. Shaked,, and M. Schwartz. 2001. Neuronal survival after CNS insult is determined by a genetically encoded autoimmune response. J. Neurosci. 21:45644571.
75. Kipnis, J.,, H. Cohen,, M. Cardon,, Y. Ziv, and, M. Schwartz. 2004. T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions. Proc. Natl. Acad. Sci. USA 101:81808185.
76. Kirjavainen, P. V.,, E. Apostolou,, T. Arvola,, S. J. Salminen,, G. R. Gibson,, and E. Isolauri. 2001. Characterizing the composition of intestinal microflora as a prospective treatment target in infant allergic disease. FEMS Immunol. Med. Microbiol. 32:17.
77. Knivsberg, A. M.,, K. L. Reichelt,, T. Hoien,, and M. Nodland. 2002. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr. Neurosci. 5:251261.
78. Kuda, T.,, T. Enomoto,, T. Yano, and, T. Fujii. 2000. Cecal environment and TBARS level in mice fed corn oil, beef tallow and menhaden fish oil. J. Nutr. Sci. Vitaminol. (Tokyo) 46:6570.
79. Kunze, W.,, Y. K. Mao,, P. Forsythe, and, J. Bienenstock. 2007. Effect of Lactobacillus sp. (Lb) probiotic ingestion on membrane properties of intrinsic sensory neurons in rat colon. Gastroenterology 132:A–401.
80. Ledochowski, M.,, B. Sperner-Unterweger, and, D. Fuchs. 1998. Lactose malabsorption is associated with early signs of mental depression in females: a preliminary report. Dig. Dis. Sci. 43:25132517.
81. Ledochowski, M.,, B. Widner,, C. Murr,, B. Sperner-Unterweger, and, D. Fuchs. 2001. Fructose malabsorption is associated with decreased plasma tryptophan. Scand. J. Gastroenterol. 36:367371.
82. Lesniewska, V.,, I. Rowland,, P. D. Cani,, A. M. Neyrinck,, N. M. Delzenne, and, P. J. Naughton. 2006. Effect on components of the intestinal microflora and plasma neuropeptide levels of feeding Lactobacillus delbrueckii, Bifidobacterium lactis, and inulin to adult and elderly rats. Appl. Environ. Microbiol. 72:65336538.
83. Linton, P. J., and, K. Dorshkind. 2004. Age-related changes in lymphocyte development and function. Nat. Immunol. 5:133139.
84. Lizko, N. N. 1987. Stress and intestinal microflora. Nahrung 31:443447.
85. Lizko, N. N. 1991. Problems of microbial ecology in man space mission. Acta Astronaut. 23:163169.
86. Logan, A. C., and, M. Katzman. 2005. Major depressive disorder: probiotics may be an adjuvant therapy. Med. Hypotheses 64:533538.
87. Lowry, C. A.,, J. H. Hollis,, A. de Vries,, B. Pan,, L. R. Brunet,, J. R. Hunt,, J. F. Paton,, E. van Kampen,, D. M. Knight,, A. K. Evans,, G. A. Rook, and, S. L. Lightman. 2007. Identification of an immune-responsive mesolimbocortical serotonergic system: potential role in regulation of emotional behavior. Neuroscience 146:756772.
88. Lu, X. Y.,, C. S. Kim,, A. Frazer,, and W. Zhang. 2006. Leptin: a potential novel antidepressant. Proc. Natl. Acad. Sci. USA 103:15931598.
89. Lydiard, R. B., and, S. A. Falsetti. 1999. Experience with anxiety and depression treatment studies: implications for designing irritable bowel syndrome clinical trials. Am. J. Med. 107:65S–73S.
90. Maassen, C. B.,, J. C. van Holten,, F. Balk,, M. J. Heijne den Bak-Glashouwer,, R. Leer,, J. D. Laman,, W. J. Boersma,, and E. Claassen. 1998. Orally administered Lactobacillus strains differentially affect the direction and efficacy of the immune response. Vet. Q. 20:S81–S83.
91. Madden, J. A., and, J. O. Hunter. 2002. A review of the role of the gut microflora in irritable bowel syndrome and the effects of probiotics. Br. J. Nutr. 88:S67–S72.
92. Maes, M.,, E. Bosmans,, R. De Jongh,, G. Kenis,, E. Vandoolaeghe,, and H. Neels. 1997. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9:853858.
93. Maes, M. 1999. Major depression and activation of the inflammatory response system. Adv. Exp. Med. Biol. 461:2546.
94. Maes, M. 2001. The immunoregulatory effects of antidepressants. Hum. Psychopharmacol. 16:95103.
95. Makino, S.,, R. A. Baker,, M. A. Smith, and, P. W. Gold. 2000. Differential regulation of neuropeptide Y mRNA expression in the arcuate nucleus and locus coeruleus by stress and anti-depressants. J. Neuroendocrinol. 12:387395.
96. Mathe, A. A.,, H. Husum,, A. El Khoury, P. Jimenez-Vasquez,, S. H. Gruber,, G. Wortwein,, G. Nikisch,, P. Baumann,, H. Agren,, W. Andersson,, A. Sodergren,, and F. Angelucci. 2007. Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role? Physiol. Behav. 92:226231.
97. McCarthy, J., L. O’Mahony,, L. O’Callaghan,, B. Sheil,, E. E. Vaughan,, N. Fitzsimons,, J. Fitzgibbon,, G. C. O’Sullivan,, B. Kiely,, J. K. Collins,, and F. Shanahan. 2003. Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance. Gut 52:975980.
98. Miller, G. E.,, C. A. Stetler,, R. M. Carney,, K. E. Freedland, and, W. A. Banks. 2002. Clinical depression and inflammatory risk markers for coronary heart disease. Am. J. Cardiol. 90:12791283.
99. Moalem, G.,, R. Leibowitz-Amit,, E. Yoles,, F. Mor,, I. R. Cohen,, and M. Schwartz. 1999. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 5:4955.
100. Montalto, M.,, V. Curigliano,, L. Santoro,, M. Vastola,, G. Cammarota,, R. Manna,, A. Gasbarrini,, and G. Gasbarrini. 2006. Management and treatment of lactose malabsorption. World J. Gastroenterol. 12:187191.
101. Moore, W. E.,, E. P. Cato, and, L. V. Holdeman. 1978. Some current concepts in intestinal bacteriology. Am. J. Clin. Nutr. 31:S33–S42.
102. Musselman, D. L.,, A. H. Miller,, M. R. Porter,, A. Manatunga,, F. Gao,, S. Penna,, B. D. Pearce,, J. Landry,, S. Glover,, J. S. McDaniel, and, C. B. Nemeroff. 2001. Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am. J. Psychiatry 158:12521257.
103. Nobaek, S.,, M. L. Johansson,, G. Molin,, S. Ahrne, and, B. Jeppsson. 2000. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am. J. Gastroenterol. 95:12311238.
104. Noverr, M. C., and, G. B. Huffnagle. 2005. The ‘microflora hypothesis’ of allergic diseases. Clin. Exp. Allergy 35:15111520.
105. O’Brien, S. M.,, P. Scully,, P. Fitzgerald,, L. V. Scott, and, T. G. Dinan. 2007. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J. Psychiatr. Res. 41:326331.
106. O’Mahony, L., J. McCarthy,, P. Kelly,, G. Hurley,, F. Luo,, K. Chen,, G. C. O’Sullivan,, B. Kiely,, J. K. Collins,, F. Shanahan, and, E. M. Quigley. 2005. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128:541551.
107. Parracho, H. M.,, M. O. Bingham,, G. R. Gibson, and, A. L. McCartney. 2005. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J. Med. Microbiol. 54:987991.
108. Reid, G.,, J. Jass,, M. T. Sebulsky, and, J. K. McCormick. 2003. Potential uses of probiotics in clinical practice. Clin. Microbiol. Rev. 16:658672.
109. Reynolds, J. L.,, T. A. Ignatowski,, R. Sud, and, R. N. Spengler. 2004. Brain-derived tumor necrosis factor-alpha and its involvement in noradrenergic neuron functioning involved in the mechanism of action of an antidepressant. J. Pharmacol. Exp. Ther. 310:12161225.
110. Robinson, J. K. 2004. Galanin and cognition. Behav. Cogn. Neurosci. Rev. 3:222242.
111. Rong, N.,, J. Selhub,, B. R. Goldin, and, I. H. Rosenberg. 1991. Bacterially synthesized folate in rat large intestine is incorporated into host tissue folyl polyglutamates. J. Nutr. 121:19551959.
112. Rustay, N. R.,, C. C. Wrenn,, J. W. Kinney,, A. Holmes,, K. R. Bailey,, T. L. Sullivan,, A. P. Harris,, K. C. Long,, M. C. Saavedra,, G. Starosta,, C. E. Innerfield,, R. J. Yang,, J. L. Dreiling, and, J. N. Crawley. 2005. Galanin impairs performance on learning and memory tasks: findings from galanin transgenic and GAL-R1 knockout mice. Neuropeptides 39:239243.
113. Schicho, R.,, D. Krueger,, F. Zeller,, C. W. Von Weyhern,, T. Frieling,, H. Kimura,, I. Ishii,, R. De Giorgio,, B. Campi,, and M. Schemann. 2006. Hydrogen sulfide is a novel prosecre-tory neuromodulator in the Guinea-pig and human colon. Gastroenterology 131:15421552.
114. Schiepers, O. J.,, M. C. Wichers, and, M. Maes. 2005. Cytokines and major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 29:201217.
115. Shanahan, F. 2002. The host-microbe interface within the gut. Best Pract. Res. Clin. Gastroenterol. 16:915931.
116. Shimizu, E.,, K. Hashimoto,, N. Okamura,, K. Koike,, N. Komatsu,, C. Kumakiri,, M. Nakazato,, H. Watanabe,, N. Shinoda,, S. Okada,, and M. Iyo. 2003. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol. Psychiatry 54:7075.
117. Sluzewska, A.,, J. K. Rybakowski,, M. Laciak,, A. Mackiewicz,, M. Sobieska,, and K. Wiktorowicz. 1995. Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Ann. N. Y. Acad. Sci. 762:474476.
118. Smits, H. H.,, A. Engering,, D. van der Kleij, E. C. de Jong,, K. Schipper,, T. M. van Capel,, B. A. Zaat,, M. Yazdanbakhsh,, E. A. Wierenga,, Y. van Kooyk, and, M. L. Kapsenberg. 2005. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J. Allergy Clin. Immunol. 115:12601267.
119. Sobko, T.,, L. Huang,, T. Midtvedt,, E. Norin,, L. E. Gustafsson,, M. Norman,, E. A. Jansson, and, J. O. Lundberg. 2006. Generation of NO by probiotic bacteria in the gastrointestinal tract. Free Radic. Biol. Med. 41:985991.
120. Sudo, N.,, Y. Chida,, Y. Aiba,, J. Sonoda,, N. Oyama,, X. N. Yu,, C. Kubo,, and Y. Koga. 2004. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 558:263275.
121. Taki, K.,, F. Takayama, and, T. Niwa. 2005. Beneficial effects of Bifidobacteria in a gastroresistant seamless capsule on hyperhomocysteinemia in hemodialysis patients. J. Ren. Nutr. 15:7780.
122. Thompson, L., and, R. C. Spiller. 1995. Impact of polyunsatu-rated fatty acids on human colonic bacterial metabolism: an in vitro and in vivo study. Br. J. Nutr. 74:733741.
123. Thorpe, A. J.,, J. P. Cleary,, A. S. Levine, and, C. M. Kotz. 2005. Centrally administered orexin A increases motivation for sweet pellets in rats. Psychopharmacology (Berlin) 182:7583.
124. Tortorella, C.,, G. Neri, and, G. G. Nussdorfer. 2007. Galanin in the regulation of the hypothalamic-pituitary-adrenal axis. Int. J. Mol. Med. 19:639647.
125. Tuglu, C.,, S. H. Kara,, O. Caliyurt,, E. Vardar, and, E. Abay. 2003. Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology (Berlin) 170:429433.
126. Uribe, A.,, M. Alam,, O. Johansson,, T. Midtvedt, and, E. Theodorsson. 1994. Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat. Gastroenterology 107:12591269.
127. Wada, E.,, K. Watase,, K. Yamada,, H. Ogura,, M. Yamano,, Y. Inomata,, J. Eguchi,, K. Yamamoto,, M. E. Sunday,, H. Maeno,, K. Mikoshiba,, H. Ohki-Hamazaki,, and K. Wada. 1997. Generation and characterization of mice lacking gastrin-releasing peptide receptor. Biochem. Biophys. Res. Commun. 239:2833.
128. Walsh, S. P., and, M. A. Kling. 2004. VNS and depression: current status and future directions. Expert Rev. Med. Devices 1:155160.
129. Wang, X.,, B. R. Wang,, X. J. Zhang,, Z. Xu,, Y. Q. Ding,, and G. Ju. 2002. Evidences for vagus nerve in maintenance of immune balance and transmission of immune information from gut to brain in STM-infected rats. World J. Gastroenterol. 8:540545.
130. Weinstein, P. D., and, J. J. Cebra. 1991. The preference for switching to IgA expression by Peyer’s patch germinal center B cells is likely due to the intrinsic influence of their microenvironment. J. Immunol. 147:41264135.
131. Wick, G.,, P. Berger,, P. Jansen-Durr, and, B. Grubeck-Loebenstein. 2003. A Darwinian-evolutionary concept of age-related diseases. Exp. Gerontol. 38:1325.
132. Wren, A. M., and, S. R. Bloom. 2007. Gut hormones and appetite control. Gastroenterology 132:21162130.
133. Wrenn, C. C.,, J. W. Kinney,, L. K. Marriott,, A. Holmes,, A. P. Harris,, M. C. Saavedra,, G. Starosta,, C. E. Innerfield,, A. S. Jacoby,, J. Shine,, T. P. Iismaa,, G. L. Wenk, and, J. N. Crawley. 2004. Learning and memory performance in mice lacking the GAL-R1 subtype of galanin receptor. Eur. J. Neurosci. 19:13841396.
134. Wrenn, C. C., and, A. Holmes. 2006. The role of galanin in modulating stress-related neural pathways. Drug News Perspect. 19:461467.
135. Yamada, K.,, E. Wada, and, K. Wada. 2000. Male mice lacking the gastrin-releasing peptide receptor (GRP-R) display elevated preference for conspecific odors and increased social investigatory behaviors. Brain Res. 870:2026.
136. Yamada, K.,, E. Wada, and, K. Wada. 2001. Female gastrin-releasing peptide receptor (GRP-R)-deficient mice exhibit altered social preference for male conspecifics: implications for GRP/GRP-R modulation of GABAergic function. Brain Res. 894:281287.
137. Yoles, E.,, E. Hauben,, O. Palgi,, E. Agranov,, A. Gothilf,, A. Cohen,, V. Kuchroo,, I. R. Cohen,, H. Weiner,, and M. Schwartz. 2001. Protective autoimmunity is a physiological response to CNS trauma. J. Neurosci. 21:37403748.
138. Zagon, A. 2001. Does the vagus nerve mediate the sixth sense? Trends Neurosci. 24:671673.
139. Ziegler, D. R.,, W. A. Cass, and, J. P. Herman. 1999. Excitatory influence of the locus coeruleus in hypothalamic-pituitary-adrenocortical axis responses to stress. J. Neuroendocrinol. 11:361369.

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